Nature Shapes Faithful and Unfaithful Brains

A reposting of an original article from January 22, 2017.

Among monogamous animals, some individuals are more faithful than others. Could these differences in fidelity be, in part, because of differences in our brains? And if so, why does this diversity in brain and behavior exist?

A snuggly prairie vole family. Photo from theNerdPatrol at Wikimedia Commons.

Prairie voles are small North American rodents that form monogamous pair bonds, share parental duties, and defend their homes. Although prairie voles form monogamous pairs, that does not mean they are sexually exclusive. About a quarter of prairie vole pups are conceived outside of their parents’ union.

Not all male prairie voles cheat on their partners at the same rates. In fact, some males are very sexually faithful. It turns out, there are both costs and benefits to being faithful and to cheating. Mariam Okhovat, Alejandro Berrio, Gerard Wallace, and Steve Phelps from the University of Texas at Austin, and Alex Ophir from Cornell University used radio-telemetry to track male prairie voles for several weeks to explore what some of these costs and benefits might be. Compared to males that only sired offspring with their own partner, unfaithful males had larger home ranges, intruded on more territories of other individuals, and encountered females more often. However, these unfaithful males were also more likely to be cheated on when they were away (probably because they were away more). I guess even rodents live by The Golden Rule.

Maps of how paired male voles in this study used space. The solid red/orange/yellow peaks show where a faithful male (in the left map) and unfaithful male (in the right map) spent their time in relation to where other paired males spent their time (showed by open blue peaks). Image from the Okhovat et al. Science paper (2015).

Vasopressin is a hormone that has been found to affect social behaviors such as aggression and pair bonding when it acts in the brain. Mariam, Alejandro, Gerard, Alex, and Steve all set out to determine how vasopressin in the brain may relate to sexual fidelity in prairie voles. They found that faithful males had lots of a particular type of vasopressin receptor (called V1aR) in certain brain areas involved in spatial memory. Surprisingly, faithful males did not have more V1aR in brain regions typically associated with pair bonding and aggression. A male that has more V1aR in spatial memory regions might better remember where his own mate is and where other males have been aggressive, which would decrease the chances that he would intrude on other territories in search of other females and increase the time that he spends home with his own mate. A male that has less V1aR in spatial memory regions might be less likely to learn from his negative experiences and more likely to sleep around.

Photos of a brain section from a faithful male (left) and unfaithful male (right). The dark shading shows the density of V1aR vasopressin receptors. The arrows show the location of the retrosplenial cortex (RSC), a brain area involved in spatial memory. Faithful males had significantly more V1aR receptors in the RSC compared to unfaithful males. Image from the Okhovat et al. Science paper (2015).

The research team then found genotype variations that related to having lots or not much V1aR in one of these spatial memory regions (called retrosplenial cortex … but we’ll just call it RSC). They confirmed these findings with a breeding study, in which they reared siblings that were genetically similar, but some had the genotype they predicted would result in lots of V1aR in RSC and some had the genotype they predicted would result in very little V1aR in RSC. They confirmed that these genetic variations correspond with the amount of vasopressin receptor in this specific spatial memory area.

The researchers then looked closer at the different versions of this vasopressin receptor gene in the RSC brain region to see if differences in the amount of vasopressin receptors in RSC may be caused by the epigenetic state of the gene (i.e. how active the gene is). They found that the genotype that results in very little V1aR in RSC had many more potential methylation sites, which can repress gene activity.

All of this data together tells a very interesting story. Male prairie voles that have the genotype for more V1aR vasopressin receptors in their RSC part of their brain are more likely to remember where their home and mate are and to remember where other aggressive prairie voles are, which will make them more likely to spend more time with their partner, to be sexually faithful and to have sexually faithful partners. Male prairie voles that have the genotype for less V1aR in their RSC are more likely to forget where their home and mate are and where other aggressive prairie voles are, which will make them more likely to cheat and to be cheated on. Overall, faithful and unfaithful male prairie voles have roughly the same number of offspring, but advantages may emerge with changes in population density. Prairie vole populations vary anywhere from 25 to 600 voles per hectare from year to year. When population densities are high, you (and your partner) are more likely to encounter more potential mates and it may benefit you to cheat (and have a “cheater’s brain”). When population densities are low, you (and your partner) are less likely to encounter more potential mates and it may benefit you to be faithful (and have a “faithful brain”). But when populations fluctuate between high and low densities, both faithful and unfaithful genotypes will get passed along from generation to generation.


Want to know more? Check this out:

Okhovat, M., Berrio, A., Wallace, G., Ophir, A., & Phelps, S. (2015). Sexual fidelity trade-offs promote regulatory variation in the prairie vole brain Science, 350 (6266), 1371-1374 DOI: 10.1126/science.aac5791

Mr. Nanny Makes Mr. Right

A reposting of an original article from November 28, 2012.

Quick! Introduce yourself to this guy before
his baby-high wears off! Photo by David
Castillo Dominici at FreeDigitalPhotos.net. 

What happens if you take a wrestler or action star and force him to babysit obnoxious but lovable kids? Well, if you’ve seen movies like The Pacifier with Vin Diesel, The Tooth Fairy with Dwayne ‘The Rock’ Johnson, Kindergarten Cop with Arnold Schwarzenegger, or The Spy Next Door with Jackie Chan, you know that he will fall madly in love both with his young charges and with the closest available woman. Hollywood is so sure of this phenomenon that they have based a whole genre of family movies on it. Now, scientists are finding that Hollywood may be on to something.

Prairie voles are one of the only 3-5% of mammals that are monogamous and in which both parents help take care of young. In females, maternal care is regulated in part by the hormones associated with pregnancy, birth and lactation. The fact that males don’t do those things and they still provide paternal care is curious. The fact that male prairie voles will often provide care to offspring that aren’t even their own is even more curious.

Will Kenkel, Jim Paredes, Jason Yee, Hossein Pournajafi-Nazarloo, Karen Bales, and Sue Carter at the University of Illinois at Chicago recently explored what happens to male prairie voles when they are exposed to unfamiliar vole pups. Male voles without any experience with females or pups were placed in a new clean cage. Then the researchers put either a pup (that was not related to the male), a dowel rod (an unfamiliar object), or nothing into the cage with them for 10 minutes. Afterwards, they measured oxytocin (a hormone associated with bonding between mothers and their offspring) and corticosterone (a stress hormone) in the males’ blood at different time points. In another study, they also looked at the activity of brain neurons associated with the production of these hormones.

A male prairie vole is startled to find a baby in his cage...

But then he takes care of it. Video by Will Kenkel.

Both adult and juvenile males exposed to a pup for 10 minutes had higher oxytocin and lower corticosterone compared to the males not exposed to a pup. But this effect was short-lived, as male hormone levels quickly evened out again. Most of these males that were exposed to a pup showed alloparental care (care of a baby that is not their own), like approaching the pup, cuddling with it and grooming it. Males with higher oxytocin and lower corticosterone levels were more attentive towards the pups. Additionally, alloparental males exposed to pups had more activity of oxytocin-producing neurons and less activity of neurons associated with corticosterone-production in a specific brain region called the paraventricular nucleus (or PVN for short).

Oxytocin is strongly associated with pair bonding in prairie voles, particularly in females, and corticosterone affects pair bonding too (generally increasing pair bonding in males and preventing it in females). If exposure to a pup affects these hormones, maybe it affects how the male would interact with adult females. To test this, the researchers put male voles in a new clean cage and put a pup, a dowel rod, or nothing into the cage with them for 20 minutes. Then they put the males with an unfamiliar adult female for 30 minutes. After getting acquainted with the female, the males were put in a “partner preference apparatus”, which has three connected chambers: a neutral center chamber, a connected chamber with the familiar female tethered into it, and a connected chamber with an unfamiliar female tethered into it. The researchers measured how much time the males spent in each of the three chambers and with each of the two females over the next 3 hours.



A prairie vole pair snuggles. Photo from Young,
Gobrogge, Liu and Wang paper in
Frontiers in Neuroendocrinology (2011)

Males that were exposed to a dowel rod or to nothing before they were introduced to a female spent equal amounts of time with each of the two females. But males that were exposed to a pup before they were introduced to a female spent nearly 4 times as much time with that female than with the unfamiliar one. In other words, hanging out with a random pup acted like Love Potion #9 on these bachelor males and made them fall for the next female they encountered! Interestingly, this effect was true not only for the males that acted in an alloparental way towards the pups, but it was also true of males that attacked the pups (The researchers quickly rescued the pups if this occurred). Perhaps, males that were alloparental with the pups had increased oxytocin and males that were aggressive with the pups had increased corticosterone, either of which would make it more likely for them to form a preference for the female they were with.

Hmm… Got your eye on a special someone? Try volunteering him to babysit before your next date.

Want to know more? Check this out:

Kenkel, W., Paredes, J., Yee, J., Pournajafi-Nazarloo, H., Bales, K., & Carter, C. (2012). Neuroendocrine and Behavioural Responses to Exposure to an Infant in Male Prairie Voles Journal of Neuroendocrinology, 24 (6), 874-886 DOI: 10.1111/j.1365-2826.2012.02301.x

The Love Chemical of 2018

Hello and welcome to the Love Chemical Pageant Results Show! The voting results are in, and today we get to crown the Love Chemical of 2018… Vasopressin! Now let’s get to know Vasopressin a little bit better.

Vasopressin (also known as Antidiuretic Hormone) is a molecule that is widely involved in the balance of water and ions (such as salts) in mammals. (Other taxonomic groups have variations of it as well). But this chemical has gone to our heads, influencing behavior as well.

In the brain, vasopressin acts on a specific receptor type, called vasopressin 1a receptor (V1aR). There are lots of V1aR receptors in brain areas that regulate social and emotional behaviors. When vasopressin binds to many of these receptors, it can result in aggression, territoriality, and fight-or-flight responses. It is also involved in the formation of memories that are necessary to avoid danger. Interestingly, males and females usually have different patterns of where in the brain these V1aR receptors are.

Although we often think of love and aggression as opposites, the life-preserving roles of vasopressin have made it well-suited to become an important chemical of love. In animals, pair bonding (the formation of a strong and unique connection between mates of a socially monogamous species) is often accompanied by an increase in aggression towards non-mates. This aggression can serve to protect the mate and family, but also to reject competitive suitors towards either partner.

Photo of a prairie vole pair from Young, Gobrogge, Liu and Wang paper
in Frontiers in Neuroendocrinology (2011)

Researchers often use several closely-related vole species to study how the brain regulates pair bonding; While prairie voles and pine voles are monogamous, raise their offspring with their partners, and defend their homes and families, montane voles and meadow voles are promiscuous and females raise their young by themselves. Oddly, giving monogamous vole species vasopressin increases their preference for spending time with their mate, their parental behaviors, and their selective aggression against outsiders, but giving promiscuous vole species vasopressin does not. Vasopressin is also more likely to increase these monogamous behaviors in males more than in females. Both males and females respond differently to vasopressin depending on their reproductive status.

It turns out, the pattern of V1aR receptors in the brain is similar between the monogamous prairie and pine voles, but different from the promiscuous montane and meadow voles. Genetic factors drive this difference, and if you alter the gene for the V1aR of a promiscuous species to be more like the prairie vole’s version of the gene, the previously promiscuous species behaves in a monogamous way! The reason promiscuous vole species don’t behave in a monogamous way when given vasopressin is because they don’t naturally have the V1aR receptors in certain brain regions to respond to it that way.

We are still learning about the role of vasopressin in pair bonding behaviors. Much of what we know has focused on these vole species, and we know much less about vasopressin’s involvement in pair bonding in other species. We also don’t know as much about the role of vasopressin in females across different reproductive stages. But one thing is for sure: Love wouldn’t be the same without Vasopressin!


Want to know more? Check these out:
Carter, C.S. (2017). The Oxytocin–vasopressin Pathway in the Context of Love and Fear. Frontiers in Endocrinology, 8(356): 1-12.

Phelps, S.M., Okhovat, M. and Berrio, A. (2017). Individual Differences in Social Behavior and Cortical Vasopressin Receptor: Genetics, Epigenetics, and Evolution. Frontiers in Endocrinology, 8(537): 1-12.

Tickerhoof, M.C. and Smith, A.S. (2017). Vasopressinergic Neurocircuitry Regulating Social Attachment in a Monogamous Species. Frontiers in Endocrinology, 8(265): 1-10.

The Love Chemical Pageant of 2018

A modified repost of an original article from February 15, 2012.

Hello and welcome to the Love Chemical Pageant of 2018! I’m your host, Miss Behavior, and YOU are the judges.

Since the beginning of…well, social animals, many hormones and neurotransmitters have been quietly working in their own ways to fill our world with love. Lately (over the last few decades), some of them have been brought out of the background and into the limelight, credited with every crush, passionate longing, parental hug, embrace among friends, and cuddle between spouses. But who truly deserves the title of The Love Chemical?

Let’s meet our contestants!

Let’s first meet our reining title-holder, Dopamine! Dopamine is a neurotransmitter produced in the brain. Sex increases dopamine levels in both males and females and blocking its effects during sex can prevent prairie voles (a monogamous species often used to test questions on pair bonding) from forming preferences for their own partner. Dopamine also plays a role in maternal and paternal behaviors.

But dopamine is not just involved in love. It has a wide range of known functions in the brain, involved in everything from voluntary movement, mood, motivation, punishment and reward, cognition, memory, learning, aggression, pain perception and sleep. Abnormally high levels of dopamine have been linked to schizophrenia and psychosis. And dopamine is especially well-known for its role in addiction... in fact, many researchers believe that we may even be addicted to our own romantic partners.

Now let’s meet Dopamine’s partner, Opioids! When natural opioids are released in the brain, they can cause a rewarding feeling that often cause us to seek more of it. When prairie voles are given drugs that prevent opioids from acting on a particular opioid receptor type (mu-opioid receptors) in a particular brain region (the caudate-putamen), they do not form pair bonds with sexual partners. Interestingly, people that see the faces of their loved ones experience lots of activity in the caudate-putamen region of the brain, especially if they rate their relationship with that person as very romantic and passionate. The caudate-putamen region of the brain also uses dopamine, so the two chemicals appear to work together there to promote the feelings of romantic love.

Please welcome Oxytocin! Oxytocin is a peptide hormone, most of which is made in the brain. Some of this oxytocin is released into the blood and affects body organs, such as the uterus and cervix during child birth and the mammary glands during breast feeding. But some of it stays in the brain and spinal cord, acting on neurons with oxytocin receptors to affect a number of behaviors. Released during child birth and nursing, oxytocin is important for helping mammalian mothers behave like moms and in species in which both parents raise young, it helps fathers behave like dads. Also released during sex, oxytocin plays an important role in pair bonding in prairie voles (particularly in the female of the pair). In humans, people given oxytocin nasal sprays have been reported to have less fear, more financial trust in strangers, increased generosity, improved memory for faces, improved recognition of social cues, and increased empathy.

But before you fall head-over-heels for oxytocin, you should know a few more things. For one thing, oxytocin isn’t exclusively linked with feel-good emotions; It has also been associated with territoriality, aggressive defense of offspring, and forming racist associations. Also, oxytocin doesn’t work alone. It has been shown to interact with vasopressin, dopamine, adrenaline and corticosterone and all these interactions affect pair bonding.

Next up is Vasopressin! Vasopressin is closely related to oxytocin. Like oxytocin receptors, vasopressin receptors are expressed in different patterns in the brains of monogamous vole species compared to promiscuous vole species. Released during sex, vasopressin plays an important role in pair bonding in monogamous prairie voles (particularly in the male of the pair). If you block vasopressin in the brain of a paired male prairie vole, he will be more likely to prefer spending time around a new female rather than his mate. On the flip side, if you increase vasopressin activity in specific brain regions of an unpaired male prairie vole or even a promiscuous male meadow vole and introduce him to a female, he will prefer spending time with her than other females. Vasopressin may also make male prairie voles more paternal.

But vasopressin does a lot of things. In the body, its primary function is to regulate water retention. In the brain, it plays a role in memory formation and territorial aggression. And even its role in monogamy is not exclusive: Vasopressin interacts with oxytocin and testosterone when working to regulate pair bonding and parental behavior.

Look out for Cortisol! Cortisol is produced by the adrenal glands (on top of the kidneys) and is involved in stress responses in humans and primates. Both men and women have increased cortisol levels when they report that they have recently fallen in love. Many studies have also found relationships between cortisol and maternal behavior in primates, but sometimes they show that cortisol increases maternal behavior and sometimes it prevents it. In rodents, where corticosterone is similar to cortisol, the story is also not very clear. Corticosterone appears to be necessary for male prairie voles to form pair bonds and it plays a role in maintaining pair bonds and promoting paternal behavior. But in female prairie voles, the opposite seems to be true! Corticosterone in females appears to prevent preference for spending time with their partner and pair bond formation.

Put your hands together for Testosterone! Testosterone is a steroid hormone and is primarily secreted from the gonads (testes in males and ovaries in females). Frequently referred to as “the male hormone”, both males and females have it and use it, although maybe a little differently. Testosterone is associated with sex drive in both men and women. But men who have recently fallen in love have lower testosterone levels than do single males, whereas women who have recently fallen in love have higher testosterone than single gals.

This is Estrogen! Estrogen is another steroid hormone, frequently referred to as “the female hormone”, although again, both males and females have it. Estrogen also seems to play a role in sex drive in both men and women. The combination of high estrogen levels and dropping progesterone levels (another steroid hormone) is critical for the development of maternal behavior in primates, sheep and rodents. But look closer and you will find that the activation of estrogen receptors in particular brain regions is associated with less sexual receptivity, parental behavior, and the preference for spending time with the mate.

So let’s have a round of applause for this year’s contenders in The Love Chemical Pageant! Now it is your turn to voice your opinion in the comments section below. Vote for the neurochemical you believe deserves the title The Love Chemical. Or suggest an alternative pageant result!


Want to know more? Check these out:

Burkett, J.P. and Young, L.J. (2012). The behavioral, anatomical and pharmacological parallels between social attachment, love and addiction. Psychopharmacology, 224:1-26.

Fisher, H.E. (1998). Lust, attraction, and attachment in mammalian reproduction. Human Nature, 9(1) 23-52.

Marazziti, D. and Canale, D. (2004). Hormonal changes when falling in love. Psychoneuroendocrinology, 29, 931-936.

Van Anders, S.M. and Watson, N.V. (2006). Social neuroendocrinology: Effects of social contexts and behaviors on sex steroids in humans. Human Nature, 17(2), 212-237.

Young, K.A., Gobrogge, K.L., Liu, Y. and Wang, Z. (2011). The neurobiology of pair bonding: Insights from a socially monogamous rodent. Frontiers in Neuroendocrinology, 32(2011), 53-69.

Addicted to Love

Image from imagerymajestic at FreeDigitalPhotos.net.

Early exposure creates a sense of euphoria, a heightening of senses, a rush of pleasure. In order to recreate and further heighten the experience, more is sought, but the euphoric effect eventually starts to wear off. Craving and palpable longing intensifies in its absence, but the effect of exposure is now a calm relief rather than a euphoric high. And once cut off abruptly and completely, desperation, grief, pain and depression set in. The pull to return to it is (almost) insurmountable.

This describes the phases of substance addiction, listed by the DSM-5, the latest version of the Diagnostic and Statistical Manual of Mental Disorders, published by the American Psychiatric Association. These phases include consumption (taking the substance), reinforcement learning (intense pleasure associated with consuming the substance), seeking more of the substance, developing a tolerance (intense pleasure is replaced with avoidance of discomfort), withdrawal (psychological and physical discomfort associated with not consuming the substance), and relapse (returning to consume the substance, even in the face of large costs of doing so).

Now re-read the first paragraph, but instead of imagining the development of a substance addiction, imagine the process of falling in love.

It sounds the same, doesn’t it? According to one theory, it sounds the same because it is the same. In essence, falling in love is the process of becoming addicted to another individual.

There are undeniable similarities between how the brain responds to substance addiction and how the brain responds to falling in love. Both substances of addiction and individuals we are attracted to cause the brain to release dopamine, a neurotransmitter, into a brain region called the nucleus accumbens. Dopamine acting in this region helps us learn to associate cues with rewarding feelings. However, dopamine acts on two different types of receptors, called D1-receptors and D2-receptors, in complex ways. Activation of D2-receptors promotes bonding with a partner; it also promotes the reward value of a substance. Activation of D1-receptors reduces bonding with a partner; it also reduces the reward value of a substance. During this time early on in a romantic relationship or early exposure to an addictive substance, dopamine is primarily acting on D2 receptors, heightening our senses and focusing our attention on the cues of our next encounter… developing our craving, our longing, our drive for the next meeting.

When we are in the early obsessive stages of love, every encounter (and especially sexual encounters) cause a pleasurable release of not just dopamine, but also natural opioids. These two brain chemicals work together in the brain to continually strengthen the association of the stimulus (the one you are falling in love with) with intense positive feelings. This will cause you to seek more and more of these interactions, craving them intensely in the times in between. These same chemicals act on the same receptors in the same way during the process of forming an addiction to a substance, causing the person to seek more and more of it.

With time, the brain adapts. Repeated encounters no longer cause the same euphoria they once did, but rather, a sense of calm contentment. The dopamine that is released before and during these encounters is now activating more of the D1-receptors, which result in less of a feeling of pleasure, and more agitation and aggression. In terms of relationships, it is thought that this transition actually helps maintain a pair bond with one individual, because in this stage you are less driven to seek a competing pair bond and you are more likely to aggressively defend the pair bond you have already established. In terms of substance abuse, this phase is called tolerance. (I know, this perspective really takes the romance out of long-term marriages, but...)

During this tolerance phase, lack of exposure to the object of your addiction (whether it is a person or a substance) results in a lack of dopamine and opioid release and an increase in stress hormone release. If we are talking about addiction to a substance, we call this withdrawal. If we are talking about a relationship, we call this separation anxiety or even heartbreak. To avoid these horrible feelings, we often relapse… right back into the arms of our addiction.

Love is not listed as a psychological disorder in the DSM-5, nor do we think of it as one. But in a true physiological sense, we may actually be addicted to the ones we love.


Want to know more? Check these out:

Burkett, J.P. and Young, L.J. (2012). The behavioral, anatomical and pharmacological parallels between social attachment, love and addiction. Psychopharmacology, 224:1-26.

Potenza, M.N. (2014). Non-substance addictive behaviors in the context of DSM-5. Addictive Behaviors, 39(1): 1-2.

The Complexities of “The Love Hormone”

New York street art. Photo in
Wikimedia Commons posted by Pedroalmovar.

Oxytocin, commonly known as “the love hormone”, is a small chemical that is produced in the brain of mammals, but can both act as a neurotransmitter and enter the blood stream and act as a hormone. It has long been heralded for its role in both maternal and romantic love, but more recent research is showing us just how complicated the physiology of love can be.

Oxytocin is released in mammalian mothers after birth. It promotes nursing and bonding between a mother and her young. As children grow, oxytocin is involved in how both mothers and fathers “baby-talk” and mirror their children. It is involved in pro-social behaviors in both young and adults: trust, generosity, cooperation, hugging, and empathy. And of course, oxytocin promotes positive communication and pair bonding in romantic couples. Countless studies have found these relationships between affiliation and oxytocin in many mammalian species, giving oxytocin its commonly used nickname “the love hormone”.

But more recent studies show that it’s not so simple.

In a number of recent studies, people have been given oxytocin nasal sprays and tested for various behavioral effects in different contexts… and the context really seems to matter. Oxytocin increases trust, generosity, cooperation, and empathy towards people we already know and like. But it decreases trust, generosity, cooperation, and empathy towards strangers. When we play games with strangers, oxytocin makes us more jealous when we lose and it makes us gloat more when we win. It also seems to enhance many attributes relating to ethnocentrism: It increases our ability to read facially-expressed emotions in people of our own race while making it harder to read facial expressions of people of a different race. When forced to choose between being nice to a stranger of our own race versus a stranger of another race, oxytocin makes us more likely to choose the person of our own race. In studies of both people and rodents, oxytocin decreases aggression towards our families and friends, but increases aggression towards strangers.

Oxytocin is not the universal love hormone we once understood it to be. It helps us direct our positive support towards our “in-groups” (our family and friends) and defend them from our “out-groups” (individuals we don’t know). It is a delicate balance: Too little of it can cause social impairment and make it difficult to connect with loved-ones; Too much of it can increase our anxiety towards strangers and racist tendencies. And to make things more complicated, each of us has a slightly different oxytocin system: sex, gender, social history, history of childhood trauma or neglect, psychiatric illnesses and genetic variations all have profound effects on the oxytocin system.

There is much we don’t know about the role of oxytocin and love. But they are a good fit, because both, it seems, are complicated.


Want to know more? Check these out:

Shamay-Tsoory SG, & Abu-Akel A (2016). The Social Salience Hypothesis of Oxytocin. Biological psychiatry, 79 (3), 194-202 PMID: 26321019

Zik JB, & Roberts DL (2015). The many faces of oxytocin: implications for psychiatry. Psychiatry research, 226 (1), 31-7 PMID: 25619431

Nature Shapes Faithful and Unfaithful Brains

Among monogamous animals, some individuals are more faithful than others. Could these differences in fidelity be, in part, because of differences in our brains? And if so, why does this diversity in brain and behavior exist?

A snuggly prairie vole family. Photo from theNerdPatrol at Wikimedia Commons.

Prairie voles are small North American rodents that form monogamous pair bonds, share parental duties, and defend their homes. Although prairie voles form monogamous pairs, that does not mean they are sexually exclusive. About a quarter of prairie vole pups are conceived outside of their parents’ union.

Not all male prairie voles cheat on their partners at the same rates. In fact, some males are very sexually faithful. It turns out, there are both costs and benefits to being faithful and to cheating. Mariam Okhovat, Alejandro Berrio, Gerard Wallace, and Steve Phelps from the University of Texas at Austin, and Alex Ophir from Cornell University used radio-telemetry to track male prairie voles for several weeks to explore what some of these costs and benefits might be. Compared to males that only sired offspring with their own partner, unfaithful males had larger home ranges, intruded on more territories of other individuals, and encountered females more often. However, these unfaithful males were also more likely to be cheated on when they were away (probably because they were away more). I guess even rodents live by The Golden Rule.

Maps of how paired male voles in this study used space. The solid red/orange/yellow peaks show where a faithful male (in the left map) and unfaithful male (in the right map) spent their time in relation to where other paired males spent their time (showed by open blue peaks). Image from the Okhovat et al. Science paper (2015).

Vasopressin is a hormone that has been found to affect social behaviors such as aggression and pair bonding when it acts in the brain. Mariam, Alejandro, Gerard, Alex, and Steve all set out to determine how vasopressin in the brain may relate to sexual fidelity in prairie voles. They found that faithful males had lots of a particular type of vasopressin receptor (called V1aR) in certain brain areas involved in spatial memory. Surprisingly, faithful males did not have more V1aR in brain regions typically associated with pair bonding and aggression. A male that has more V1aR in spatial memory regions might better remember where his own mate is and where other males have been aggressive, which would decrease the chances that he would intrude on other territories in search of other females and increase the time that he spends home with his own mate. A male that has less V1aR in spatial memory regions might be less likely to learn from his negative experiences and more likely to sleep around.

Photos of a brain section from a faithful male (left) and unfaithful male (right). The dark shading shows the density of V1aR vasopressin receptors. The arrows show the location of the retrosplenial cortex (RSC), a brain area involved in spatial memory. Faithful males had significantly more V1aR receptors in the RSC compared to unfaithful males. Image from the Okhovat et al. Science paper (2015).

The research team then found genotype variations that related to having lots or not much V1aR in one of these spatial memory regions (called retrosplenial cortex … but we’ll just call it RSC). They confirmed these findings with a breeding study, in which they reared siblings that were genetically similar, but some had the genotype they predicted would result in lots of V1aR in RSC and some had the genotype they predicted would result in very little V1aR in RSC. They confirmed that these genetic variations correspond with the amount of vasopressin receptor in this specific spatial memory area.

The researchers then looked closer at the different versions of this vasopressin receptor gene in the RSC brain region to see if differences in the amount of vasopressin receptors in RSC may be caused by the epigenetic state of the gene (i.e. how active the gene is). They found that the genotype that results in very little V1aR in RSC had many more potential methylation sites, which can repress gene activity.

All of this data together tells a very interesting story. Male prairie voles that have the genotype for more V1aR vasopressin receptors in their RSC part of their brain are more likely to remember where their home and mate are and to remember where other aggressive prairie voles are, which will make them more likely to spend more time with their partner, to be sexually faithful and to have sexually faithful partners. Male prairie voles that have the genotype for less V1aR in their RSC are more likely to forget where their home and mate are and where other aggressive prairie voles are, which will make them more likely to cheat and to be cheated on. Overall, faithful and unfaithful male prairie voles have roughly the same number of offspring, but advantages may emerge with changes in population density. Prairie vole populations vary anywhere from 25 to 600 voles per hectare from year to year. When population densities are high, you (and your partner) are more likely to encounter more potential mates and it may benefit you to cheat (and have a “cheater’s brain”). When population densities are low, you (and your partner) are less likely to encounter more potential mates and it may benefit you to be faithful (and have a “faithful brain”). But when populations fluctuate between high and low densities, both faithful and unfaithful genotypes will get passed along from generation to generation.


Want to know more? Check this out:

Okhovat, M., Berrio, A., Wallace, G., Ophir, A., & Phelps, S. (2015). Sexual fidelity trade-offs promote regulatory variation in the prairie vole brain Science, 350 (6266), 1371-1374 DOI: 10.1126/science.aac5791

Dogs Have Co-opted Our Physiology to Win Our Hearts

Photo by Roberto Ferrari at Wikimedia Commons.

Why do we feel genuine love and friendship for our dogs? The social relationship between humans and dogs is not just special, it is downright AMAZING! Domestic dogs are the only species that we know of that will spontaneously respond to cooperative human gestures, such as pointing or gazing in a specific direction, without any training or prior experience. Wolves and even non-human great apes require extensive experience with people to understand these human gestures. Dogs, on the other hand, are so naturally in-tune with our gestures that they, like human children, are likely to interpret eye contact as communicative, even when it is not. New research has found that eye contact between ourselves and our canine companions may fuel an interspecies physiological feedback loop that keeps our two species living as best friends.

Today at Accumulating Glitches, I am exploring new research about how our four-legged best friends change our brain physiology so we will love and care for them more. Check out the full story here. 

And this is why we love our dogs so much:

Further reading:
MacLean, E.L. and Hare, B. Dogs hijack the human bonding pathway, Science, 438:6232, 280-281 (2015). DOI: 10.1126/science.aab1200

Nagasawa, M., Mitsui, S., En, S., Ohtani, N., Ohta, M., Sakuma, Y., Onaka, T., Mogi, K.., and Kikusui, T. Oxytocin-gaze positive loop and the coevolution of human-dog bonds, Science, 438:6232, 333-336 (2015). DOI:10.1126/science.1261022

Your Picks of 2012

This has been a wild first year for The Scorpion and the Frog. I have enjoyed sharing the world of animal physiology and behavior research with you. But even more, I have enjoyed hearing from you about your experiences, thoughts and perspectives.

I gathered data on page visits, comments, and social media attention for The Scorpion and the Frog posts and have determined your top five posts of the year. Here are Your Favorite The Scorpion and the Frog Posts of 2012 (in no particular order).

1. The “Love Hormone” Pageant pits six hormones against one another in a contest for the title of the “Love Hormone”. The "Love Hormone" of 2012 focuses on the big winner (as determined by reader votes), Dopamine!

2. Scientists put the philosophical question, “What Do Animals Think of Their Dead?” to the test. Their results may surprise you!

3. In Snakes Deceive to Get a Little Snuggle, we learn about boy snakes pretending to be sexy girl snakes, all in the hopes of a good cuddle.

4. Male nursery web spiders give silk-wrapped gifts to the girls that catch their eyes. But why waste a perfectly good present when a piece of junk in clever packaging will do? Sex, Lies and Spider Silk tells the story of these deceptive gift-givers.

5. Don’t Challenge a Fruit-Eating Bat to a Drinking Contest. Just don’t. Here’s why.

Thank you for your support and participation over the year. Next year should be full of new wacky animal stories. (And if you’d like to see my 2012 picks for my favorite animal physiology and behavior blog posts at other sites, click here).

Mr. Nanny Makes Mr. Right

Quick! Introduce yourself to this guy before
his baby-high wears off! Photo by David
Castillo Dominici at FreeDigitalPhotos.net. 

What happens if you take a wrestler or action star and force him to babysit obnoxious but lovable kids? Well, if you’ve seen movies like The Pacifier with Vin Diesel, The Tooth Fairy with Dwayne ‘The Rock’ Johnson, Kindergarten Cop with Arnold Schwarzenegger, or The Spy Next Door with Jackie Chan, you know that he will fall madly in love both with his young charges and with the closest available woman. Hollywood is so sure of this phenomenon that they have based a whole genre of family movies on it. Now, scientists are finding that Hollywood may be on to something.

Prairie voles are one of the only 3-5% of mammals that are monogamous and in which both parents help take care of young. In females, maternal care is regulated in part by the hormones associated with pregnancy, birth and lactation. The fact that males don’t do those things and they still provide paternal care is curious. The fact that male prairie voles will often provide care to offspring that aren’t even their own is even more curious.

Will Kenkel, Jim Paredes, Jason Yee, Hossein Pournajafi-Nazarloo, Karen Bales, and Sue Carter at the University of Illinois at Chicago recently explored what happens to male prairie voles when they are exposed to unfamiliar vole pups. Male voles without any experience with females or pups were placed in a new clean cage. Then the researchers put either a pup (that was not related to the male), a dowel rod (an unfamiliar object), or nothing into the cage with them for 10 minutes. Afterwards, they measured oxytocin (a hormone associated with bonding between mothers and their offspring) and corticosterone (a stress hormone) in the males’ blood at different time points. In another study, they also looked at the activity of brain neurons associated with the production of these hormones.

A male prairie vole is startled to find a baby in his cage...
But then he takes care of it. Video by Will Kenkel.

Both adult and juvenile males exposed to a pup for 10 minutes had higher oxytocin and lower corticosterone compared to the males not exposed to a pup. But this effect was short-lived, as male hormone levels quickly evened out again. Most of these males that were exposed to a pup showed alloparental care (care of a baby that is not their own), like approaching the pup, cuddling with it and grooming it. Males with higher oxytocin and lower corticosterone levels were more attentive towards the pups. Additionally, alloparental males exposed to pups had more activity of oxytocin-producing neurons and less activity of neurons associated with corticosterone-production in a specific brain region called the paraventricular nucleus (or PVN for short).

Oxytocin is strongly associated with pair bonding in prairie voles, particularly in females, and corticosterone affects pair bonding too (generally increasing pair bonding in males and preventing it in females). If exposure to a pup affects these hormones, maybe it affects how the male would interact with adult females. To test this, the researchers put male voles in a new clean cage and put a pup, a dowel rod, or nothing into the cage with them for 20 minutes. Then they put the males with an unfamiliar adult female for 30 minutes. After getting acquainted with the female, the males were put in a “partner preference apparatus”, which has three connected chambers: a neutral center chamber, a connected chamber with the familiar female tethered into it, and a connected chamber with an unfamiliar female tethered into it. The researchers measured how much time the males spent in each of the three chambers and with each of the two females over the next 3 hours.



A prairie vole pair snuggles. Photo from Young,
Gobrogge, Liu and Wang paper in
Frontiers in Neuroendocrinology (2011)

Males that were exposed to a dowel rod or to nothing before they were introduced to a female spent equal amounts of time with each of the two females. But males that were exposed to a pup before they were introduced to a female spent nearly 4 times as much time with that female than with the unfamiliar one. In other words, hanging out with a random pup acted like Love Potion #9 on these bachelor males and made them fall for the next female they encountered! Interestingly, this effect was true not only for the males that acted in an alloparental way towards the pups, but it was also true of males that attacked the pups (The researchers quickly rescued the pups if this occurred). Perhaps, males that were alloparental with the pups had increased oxytocin and males that were aggressive with the pups had increased corticosterone, either of which would make it more likely for them to form a preference for the female they were with.

Hmm… Got your eye on a special someone? Try volunteering him to babysit before your next date.

Want to know more? Check this out:

Kenkel, W., Paredes, J., Yee, J., Pournajafi-Nazarloo, H., Bales, K., & Carter, C. (2012). Neuroendocrine and Behavioural Responses to Exposure to an Infant in Male Prairie Voles Journal of Neuroendocrinology, 24 (6), 874-886 DOI: 10.1111/j.1365-2826.2012.02301.x

Uncontrollable Love: A Guest Post

By Yunhan Zhao

Image from Freedigitalphotos.net

What is love? Under Shakespeare’s leather pen, love is the tragedy of Romeo and Juliet. In the poet’s eyes, love is the courage of Paris to elope with Helen and stand against the world. In Pretty Woman love doesn’t care about social status or wealth. When people fall in love the whole world feels brighter and more vibrant. Orpheus and Eurydice, Jane Eyre and Rochester, Darcy and Elizabeth…thousands of romantic stories, poems and songs illustrate the countless versions of love tales. Now scientists have revealed their scientific version of the love tale. They say love is comprised of magic chemicals interacting with our brains.

Photo of a prairie vole pair from Young,
Gobrogge, Liu and Wang paper in
Frontiers in Neuroendocrinology (2011)

In 1999, researchers Mary M. Cho, Courtney De Vries, Jessie Williams and Sue Carter at the University of Maryland conducted NIMH funded research aimed to unlock the secret behind ‘love.’ By using the monogamous prairie vole (Microtus ochrogaster) as subjects, they investigated the important neurophysiological events that contribute to the development and maintenance of pair bonding between heterosexual adults. Here they designed an experiment to test the hypothesis that oxytocin and vasopressin (chemicals that are released in the brain during sexual behavior) facilitate the development of partner preference.

In their experiments, the researchers randomly assigned prairie voles to three different dose groups of oxytocin, three different dose groups of vasopressin and a control group which used cerebrospinal fluid. After receiving injections directly to their brains, each prairie vole was housed with an opposite sex partner for one hour (referred as cohabitation below). Then partner preference was assessed immediately by measuring the time spent in physical contact with either the familiar partner or a stranger vole.

Researchers found that the test subjects made stronger partner preferences depending on which kind of injection they received. As expected, results showed that in male prairie voles, almost all the vasopressin and oxytocin treatments (except the lowest dose of oxytocin) led to a loyal choice for the cohabiting partners over an unacquainted female. In females, however, only the highest dose of vasopressin and oxytocin treatments resulted in a loyal choice. In contrast, with the cerebrospinal fluid control treatment in both genders of voles, the test voles were always equally attracted to their previous partners and the unacquainted strangers.

Partner preferences of male (left) and female (right) after receiving different injections.
OT = oxytocin, AVP = vasopressin, CTL = cerebrospinal fluid. Figure from Cho, M.,
DeVries, A., Williams, J., & Carter, C. (1999). The effects of oxytocin and vasopressin
on partner preferences in male and female prairie voles (Microtus ochrogaster).
Behavioral Neuroscience, 113(5), 1071-1079.

This experiment found that high doses of both vasopressin and oxytocin may indeed associate with high partner fidelity in both gender of prairie voles. However, are these two chemicals the love elements in humans as well? Does it mean in the near future people can prevent divorces with only a few chemical injections to their spouses? The answer is still not clear. Especially since scientists have recently revealed that vasopressin and oxytocin may relate to distress in pair-bonded human relationships.

Shelly Taylor, Shimon Saphire-Bernstein and Teresa Seeman from the University of California, Los Angeles assessed 85 young adults in committed relationships. They asked participants to complete a series of self-reported questionnaires which included items like “how often they argue with you,” “how often they criticize you,” and “how often they get on your nerves”. Additionally, they also had the participants’ blood drawn within a week of finishing the assessments.

Image from Freedigitalphotos.net

Analysis showed that the elevated plasma oxytocin levels were associated with relationship distress in women while the increased plasma vasopressin levels were associated with relationship distress in men. But what should be noticed is that the direction of such effects remains unknown. Although no evidence revealed the exact relationship between humans’ plasma vasopressin and oxytocin levels and relationship distress, it appears that these two chemicals may be associated with very different emotional effects in voles and humans. However, an alternative explanation could also be that oxytocin and vasopressin contribute differently in different stages or contexts of romantic relationships.

Love seems uncontrollable even in the scientific world. Prairie voles crave emotional and sexual union after being injected with a high level of oxytocin and vasopressin into their brains, but people with the high presence of the same chemicals become vulnerable to relationship problems. So what is the key here?

References

1. Cho, M., DeVries, A., Williams, J., & Carter, C. (1999). The effects of oxytocin and vasopressin on partner preferences in male and female prairie voles (Microtus ochrogaster) Behavioral Neuroscience, 113 (5), 1071-1079 DOI: 10.1037//0735-7044.113.5.1071

2. Taylor, S.E., Saphire-Bernstein, S., & Seeman, T.E. (2009). Are Plasma Oxytocin in Women and Plasma Vasopressin in Men Biomarkers of Distressed Pair-Bond Relationships? Psychological Science, 2010 (21), 3-7 DOI: 10.1177/0956797609356507

The "Love Hormone" of 2012

Hello and welcome to the Love Hormone Pageant Results Show!  You have cast your votes, the results are in, and the “Love Hormone” of 2012 is… (dramatic pause)… Dopamine!

Dopamine is arguably the most exciting of love hormones. A neurotransmitter produced in the brain, dopamine plays a key role in many motivated behaviors (and love, especially falling in love, involves a lot of motivated behavior). It does this mostly through the mesolimbic reward system, which largely consists of dopamine-producing neuron cells in a brain region called the ventral tegmental area and their projections to other brain regions, including the nucleus accumbens. The mesolimbic reward system exists and has been studied in mammals, birds, reptiles and fish, but the story of how dopamine may be involved in “love” has been explored most with one particular mammal species, the prairie vole.

Photo of a prairie vole pair from Young, Gobrogge, Liu
and Wang paper in Frontiers in Neuroendocrinology (2011)

The prairie vole is a small rodent from the grasslands of the central United States. Unlike approximately 97% of mammal species, prairie voles are socially monogamous and form long-term pair bonds. Male and female pairs travel together, nest together and share parenting duties. Pairs tend to stay together for life and when one partner dies, the surviving partner may never re-pair with a new mate. The role that dopamine plays in how these pair bonds are formed between prairie vole couples has been studied extensively over the last 13 years by Zuoxin Wang at Florida State University and over 30 of his colleagues. Kimberly Young, Kyle Gobrogge, Yan Liu and Zuoxin Wang summarize much of this work in a recent review.

Graph showing that prairie voles prefer to
spend time with their partner after 24 hours
of living together and mating:fromYoung,
Gobrogge, Liu and Wang paper in
Frontiers in Neuroendocrinology (2011)

If you put a virgin male and a virgin female prairie vole in an enclosure and let them live together and mate for 24 hours, they will reliably prefer to spend time with each other rather than with a stranger if given that choice – this is called partner preference. If you enhance dopamine action in the brain, this partner preference will happen even sooner and if you block dopamine receptors throughout the brain, it won’t happen at all. This pattern is even true if you change dopamine action only in the nucleus accumbens, showing that dopamine binding in the nucleus accumbens is critical for the formation of partner preference and pair bonds.

The effect of a hormone or neurotransmitter is completely dependent on its receptors: where they are, how many there are, and how well things bind to them. Dopamine receptors can be classified into two main families, called D1-like and D2-like receptors, and they often have opposite effects. For example, in the prairie vole nucleus accumbens, activating D2 receptors or blocking D1 receptors will cause partner preference to form faster, whereas blocking D2 receptors or activating D1 receptors will prevent it from forming at all. Furthermore, male prairie voles develop more D1 receptors in the nucleus accumbens during pair bonding, which likely work to prevent the animal from forming a pair bond with a second female and keeping him faithful to his mate. Interestingly, promiscuous meadow voles generally have more D1-like receptors in the nucleus accumbens than closely related but monogamous prairie voles. So in the prairie vole nucleus accumbens, activation of D2 receptors promotes the formation of pair bonds and activation of D1 receptors prevents the formation of pair bonds.

However, dopamine is not all roses and chocolate hearts. The action of dopamine in the mesolimbic reward system, and especially in the nucleus accumbens, regulates much more than pair bonding; It regulates a whole suite of motivated social behaviors, like sexual, parental, play, and aggressive behaviors, as well as other motivated behaviors, like seeking food and drugs of addiction. Furthermore, mesolimbic dopamine seems to be at the heart of the interactions between drugs of abuse and social behavior. In another recent review by the same research group, Wang and his colleagues point out that brief exposure to any known drug of abuse activates dopamine activity in the nucleus accumbens and repeated drug exposure causes long-lasting or permanent changes to mesolimbic reward brain areas like the nucleus accumbens. For example, repeated exposure to psychostimulants increases the number and sensitivity of D1 receptors in the nucleus accumbens…Wait, what do active D1 receptors in the nucleus accumbens do? Oh yeah, they prevent pair bonding and partner preference formation. And not surprisingly, giving amphetamine (a psychostimulant) to prairie voles prevents them from forming partner preferences and pair bonds. So if you don’t want to hurt your chances of falling in love some day, just say “No” to drugs, mmmkay?

Dopamine is a busy neurohormone: It is not only involved in love and motivated behaviors, but is also involved in everything from voluntary movement, mood, punishment and reward, cognition, memory, learning, aggression, pain perception and sleep. It is also important to keep in mind that dopamine does not work alone. To regulate pair bonding and partner preference, dopamine interacts with oxytocin, vasopressin, glutamate, GABA, and corticotrophin-releasing factor. But then again, love is about as complex a brain function as you can get – we couldn’t expect a single hormone to go it alone!

So put your hands together one last time to celebrate the “Love Hormone” of 2012: Dopamine!

Want to know more? Check these out:

Young, K., Gobrogge, K., Liu, Y., & Wang, Z. (2011). The neurobiology of pair bonding: Insights from a socially monogamous rodent Frontiers in Neuroendocrinology, 32 (1), 53-69 DOI: 10.1016/j.yfrne.2010.07.006

Young, K., Gobrogge, K., & Wang, Z. (2011). The role of mesocorticolimbic dopamine in regulating interactions between drugs of abuse and social behavior Neuroscience & Biobehavioral Reviews, 35 (3), 498-515 DOI: 10.1016/j.neubiorev.2010.06.004