It Feels Good When You Sing a Song (In Fall)

A repost of an original article published October 3, 2012.

Most male songbirds will sing when they see a pretty female during the breeding season. But some male songbirds sing even when it’s not the breeding season. Why do so many birds sing in fall at all?

Maybe singing feels good… But how do you ask a bird if it feels good to sing? European starlings are one of those bird species that sing both in spring (the breeding season) and in fall (not the breeding season). Lauren Riters, Cindi Kelm-Nelson, and Sharon Stevenson at the University of Wisconsin at Madison did a series of ingenious experiments to ask starlings if and when it feels good to sing.

A European starling sings his fall-blues away. Photo by Linda Tanner at Wikimedia.

Psychologists have long used a paradigm called conditioned place preference (CPP) to evaluate whether an animal finds something rewarding or pleasurable. CPP is based on the idea that if an animal experiences something meaningless while at the same time experiencing something else that is rewarding, the animal will learn to associate these two things with each other in a phenomenon called conditioning. For example, a puppy that has learned that every time it sits it gets a treat, will find itself sitting more often.

A researcher can also compare how rewarding different types of treats are. If we want to know if puppies like carrots or steak better, we can give one group of puppies a carrot every time they sit and another group of puppies a piece of steak every time they sit. If the group of puppies that are conditioned with steak spend more time sitting, we can conclude that steak is more rewarding to puppies than carrots are.

Lauren and Sharon used this principle to ask starlings if singing is rewarding. They put spring starlings in a cage with a nestbox and a female and let them sing away, while counting how many songs they sang in 30 minutes. Then they immediately put them in another cage that was decorated with yellow materials on one side and green materials on the other, but they restricted each bird to only one of the two colored sides. This is the conditioning phase in which the bird learns to associate the colored cage with the feeling they get from singing.

The next day, they put the starlings in the yellow and green cage without restrictions so they could choose what side they wanted to hang out in. If singing is rewarding, we would expect starlings that sang a lot to spend more time on the side with the color they were placed in the day before.



Do people that sing in the car spend more time in the car?
Photo by freedigitalphotos.net.

That didn’t happen. The spring starlings spent the same amount of time in the yellow or green side of the cage regardless of how much they sang the day before.

But when Lauren and Sharon did the same test with fall starlings singing without a female, there has a huge effect: Males that sang more spent much more time on the colored side of the cage they were placed in the day before. Singing, for a male starling, is apparently rewarding in fall, but not in spring.

This result actually makes a lot of sense. In spring, males sing to attract and court females, so they are rewarded by the feeling they get from the female’s response, not from the act of singing itself. But in fall, males are not attracting females. So why do they sing in fall? Because it feels good.

It looks like Sesame Street got it right with their 1970s song “It Feels Good When You Sing a Song”:

You can't go wrong
when you're singing a song
Sing it loud, sing it strong
It feels good when you sing a song

But why does singing feel good? At least some of the reason, it seems, is opioids. Not quite what Sesame Street had in mind, but hey.

Despite their reputation for being one of the world’s oldest drugs, many opioids are naturally occurring neuropeptides (brain chemicals). They are involved in pain relief and euphoria, commonly combined in the phenomenon of runner’s high. Could opioids be involved in the feel-good sensation created by singing? Maybe.

Cindi, Sharon and Lauren suspect that singing in fall causes male starlings to release opioids in their little brains, which makes singing more rewarding and makes them want to sing more. But how do we know how much opioid an animal has in its brain? Hmmm… Opioids cause analgesia (pain relief). Therefore, if singing a lot in fall releases more opioids, then birds that sing a lot in fall should be more pain-tolerant, right? The researchers let male starlings sing and counted how many songs they produced for 20 minutes. Then they dipped their foot in uncomfortably warm water and timed how long it took for the bird to pull its toes out. Fall males that sang more took longer to pull their feet out of the birdy foot-spa than did the males that sang less.

Interestingly, if you give starlings a drug to enhance opioids, they leave their feet in the foot-spa longer than if you give them a drug to block opioids. So it seems that singing in fall increases pain tolerance in the same way that opioids do, likely because the act of singing in fall causes the brain to release its own opioids. (Although it is also possible that birds that produce more opioids feel like singing more).

And what about singing in spring? When Cindi, Sharon and Lauren repeated the study with spring starlings, these birds did not get pain relief from singing. Again, they are probably rewarded by their interactions with females and not the act of singing.

So if you ever find yourself in pain, just

Sing
Sing a song
Make it simple
To last your whole life long
Don't worry that it's not good enough
For anyone else to hear
Sing
Sing a song
La la la la la la la la la la la
La la la la la la la

Want to know more? Check these out:

1. Riters LV, & Stevenson SA (2012). Reward and vocal production: song-associated place preference in songbirds. Physiology & Behavior, 106 (2), 87-94 PMID: 22285212

2. Kelm-Nelson, C.A., Stevenson, S.A., & Riters, L.V. (2012). Context-dependent links between song production 1 and opioid-mediated analgesia in male European starlings (Sturnus vulgaris) PLOS One, 7 (10)

3. Riters LV, Schroeder MB, Auger CJ, Eens M, Pinxten R, & Ball GF (2005). Evidence for opioid involvement in the regulation of song production in male European starlings (Sturnus vulgaris). Behavioral neuroscience, 119 (1), 245-55 PMID: 15727529

4. Kelm CA, Forbes-Lorman RM, Auger CJ, & Riters LV (2011). Mu-opioid receptor densities are depleted in regions implicated in agonistic and sexual behavior in male European starlings (Sturnus vulgaris) defending nest sites and courting females. Behavioural brain research, 219 (1), 15-22 PMID: 21147175

Does Social Status Change Brains?

A reposting of an original article in The Scorpion and the Frog.

Photo by The Grappling Source Inc.
at Wikimedia Commons

Being subordinated is stressful. The process of one individual lowering the social rank of another often involves physical aggression, aggressive displays, and exclusion. In addition to the obvious possible costs of being subordinated (like getting beat up), subordinated individuals often undergo physiological changes to their hormonal systems and brains. Sounds pretty scary, doesn’t it? But what if some of those changes are beneficial in some ways?

Dominance hierarchies are a fact of life across the animal kingdom. In a social group, everyone can’t be dominant (otherwise, life would always be like an episode of Celebrity Apprentice, and what could possibly be more stressful than that?). Living in a social group is more peaceful and nutritive when a clear dominance hierarchy is established.

Establishing that hierarchy often involves a relatively short aggressive phase of jostling for position, followed by a longer more stable phase once everyone knows where they fall in the social group. Established dominance hierarchies are not always stable (they can change over time or from moment to moment) and they are not always linear (for example, Ben can be dominant over Chris, who is dominant over David, who is dominant over Ben). But they do generally help reduce conflict and the risk of physical injury overall.

Nonetheless, it can be stressful to be on the subordinate end of a dominance hierarchy and these social interactions are known to cause physiological changes. Researchers Christina Sørensen and Göran Nilsson from the University of Oslo, Cliff Summers from the University of South Dakota and Øyvind Øverli from the Norwegian University of Life Sciences investigated some of these physiological differences among isolated, dominant, and subordinate rainbow trout.

A photo of a rainbow trout by Ken Hammond at the USDA.
Photo at Wikimedia Commons.

Like other salmonid fish, rainbow trout are aggressive, territorial and develop social hierarchies as juveniles. Dominant trout tend to initiate most of the aggressive acts, hog food resources, grow larger, and reproduce the most, whereas subordinate trout display less aggression, feeding, growth, and reproduction. The researchers recorded the behavior, feeding and growth rates in three groups of fish: trout housed alone, trout housed with a more subordinate trout, and trout housed with a more dominant trout. The researchers also measured cortisol (a hormone involved in stress responses), serotonin (a neurotransmitter involved in mood, the perception of food availability, and the perception of social rank, among other things) and the development of new neurons (called neurogenesis) in these same fish.

This video of two juvenile rainbow trout was taken by Dr. Erik Höglund. Here is Christina Sørensen’s description of the video: “What you see in the film is two juvenile rainbow trout who have been housed on each side of a dividing wall in a small aquarium. The dividing wall has been removed (for the first time) immediately before filming. You will see that the fish initially show interest for each other, followed by a typical display behaviour, where they circle each other. Finally one of the fish will initiate aggression by biting the other. First the aggression is bidirectional, as they fight for dominance, but after a while, one of the fish withdraws from further aggression and shows only submissive behaviour (escaping from the dominant and in the long run trying to hide... and as is described in the paper, depressed feed intake). The video has been cut to show in quick succession these four stages of development of the dominance hierarchy”.

The researchers found that as expected, the dominant trout were aggressive when a pair was first placed together, but the aggression subsided after about 3 days. Also as expected, the dominant and isolated trout were bold feeders with low cortisol levels and high growth rates, whereas the subordinate trout did not feed as well, had high cortisol levels and low growth rates. Additionally, the subordinate trout had higher serotonin activity levels and less neurogenesis than the dominant or isolated trout. These results suggest that the subordination experience causes significant changes to trout brain development (Although we can’t rule out the possibility that fish with more serotonin and less neurogenesis are predisposed to be subordinate). In either case, this sounds like bad news for subordinate brains, right? Maybe it is. Or maybe the decrease in neurogenesis just reflects the decrease in overall growth rates (smaller bodies need smaller brains). Or maybe something about the development of these subordinate brains improves the chances that these individuals will survive and reproduce in their subordination.

A crayfish raising its claws. Image by Duloup at Wikimedia.

Research on dominance in crayfish by Fadi Issa, Joanne Drummond, and Don Edwards at Georgia State University and Daniel Cattaert at the University of Bordeaux helps shed light on this third possibility. Crayfish (which are actually not fish at all, but are freshwater crustaceans that look like small lobsters) form long-lasting and stable social hierarchies. If you poke a crayfish in the side, an isolated or dominant crayfish will turn towards whatever poked it and raise its posture and claws to confront it; A subordinate crayfish will do one of two maneuvers that involves lowering the posture and backing away from whatever poked it. Furthermore, dominant and subordinate crayfish have different neuronal activity patterns in response to being poked, and part of this difference involves differences in the activity of serotonergic neurons.

It appears that the brains of dominant and subordinate individuals function differently and part of this difference involves serotonin. This may help dominant animals to continue to behave in a dominant fashion and subordinate individuals to continue to behave in a subordinate fashion, thereby preserving the peace for the whole social group.

Want to know more? Check these out:

1. Sørensen, C., Nilsson, G., Summers, C., & Øverli, �. (2012). Social stress reduces forebrain cell proliferation in rainbow trout (Oncorhynchus mykiss) Behavioural Brain Research, 227 (2), 311-318 DOI: 10.1016/j.bbr.2011.01.041

2. Issa, F., Drummond, J., Cattaert, D., & Edwards, D. (2012). Neural Circuit Reconfiguration by Social Status Journal of Neuroscience, 32 (16), 5638-5645 DOI: 10.1523/JNEUROSCI.5668-11.2012

3. Yeh, S., Fricke, R., & Edwards, D. (1996). The Effect of Social Experience on Serotonergic Modulation of the Escape Circuit of Crayfish Science, 271 (5247), 366-369 DOI: 10.1126/science.271.5247.366

4. Issa, F., & Edwards, D. (2006). Ritualized Submission and the Reduction of Aggression in an Invertebrate Current Biology, 16 (22), 2217-2221 DOI: 10.1016/j.cub.2006.08.065

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

Cow Pies Can Make You Smarter and Less Stressed

A reposting of an article from August, 2015

It seems like everyone is running around buying school supplies and books, registering for classes, and fretting about how hard it is going to be to learn another whole year’s worth of stuff. The secret to success, it turns out, may lie in cow dung.

A cow pie. Photo taken by Jeff Vanuga at
the USDA available at Wikimedia Commons.

Recent research has highlighted the important role that microbes living in animal digestive tracts have on host animals’ health and behavior. This influence of our gut microbes on our behavior is called the microbiota-gut-brain axis. Many of these microbes have long-standing populations that reproduce and spend their whole lives in our guts. Because our digestive tracts do not have much oxygen, these species are anaerobic (do not require oxygen to live). However, our gut communities also have more transient aerobic members (species that do require oxygen to live) that come in when they are ingested and die or leave with the droppings. One of these transient aerobic intestinal citizens is Mycobacterium vaccae (or M. vaccae for short), an aerobic bacterium that naturally lives in soil, water, and yes, cow dung.

When mice are injected with heat-killed M. vaccae, they develop an immune response that activates their brain serotonin system and reduces signs of stress. Serotonin is a neurotransmitter that is found in the brain and is involved in regulating alertness, mood, learning and memory. In fact, many antidepressant drugs work by increasing the amount of available serotonin in the brain. Interestingly, serotonin is also found in the digestive system, where it plays a role in digestive health. Since M. vaccae can increase serotonin function, and serotonin reduces anxiety and improves learning, researchers Dorothy Matthews and Susan Jenks at The Sage Colleges in New York set out to test whether eating live M. vaccae could reduce anxiety and improve learning in mice.

A drawing of the mouse maze used by Dorothy and Susan.
This image is from their 2013 Behavioural Processes paper.

The researchers developed a Plexiglas mouse-maze with three difficulty levels, where each increase in difficulty was marked by more turns and a longer path. They encouraged the mice to run the maze by placing a tasty treat (a square of peanut butter on Wonder Bread™) at the end of the maze. Half of the mice were given live M. vaccae on the peanut butter and bread treat three weeks and one week before running the maze, and then again on each treat at the end of each maze run. The other half were given peanut butter and bread without the bacterial additive. The mice then ran the maze roughly every other day: four times at level 1, four times at level 2 and four times at level 3. Each maze run was video recorded and the researchers later watched the videos to count stress-related behaviors.

The mice that ingested M. vaccae on their peanut butter sandwiches completed the maze twice as fast as those that ate plain peanut butter sandwiches. They also had fewer stress-related behaviors, particularly at the first difficulty level of the maze when everything was new and scary. In general, the fewer stress behaviors a mouse did, the faster its maze-running time was. The mice that ate the M. vaccae also tended to make fewer mistakes.

The researchers then wanted to know how long the effects of M. vaccae lasted. They continued to test the mice in the same maze, again with four runs at level 1, four runs at level 2 and four runs at level 3, but for these maze runs no one was given the M. vaccae. The mice that had previously eaten the M. vaccae continued to complete the maze faster and with fewer mistakes and to show fewer stress-related behaviors for about the first week before the M. vaccae effects wore off.

What does this all mean? It means eating dirt isn’t all bad (although I don't recommend eating cow poop). Letting yourself get a bit dirty and ingesting some of nature's microbes could even help you learn better, remember more, and stay calm - especially in new situations. Just something to think about as the school year gets started.


Want to know more? Check these out:

1. Matthews, D., & Jenks, S. (2013). Ingestion of Mycobacterium vaccae decreases anxiety-related behavior and improves learning in mice Behavioural Processes, 96, 27-35 DOI: 10.1016/j.beproc.2013.02.007

2. Lowry, C., Hollis, J., de Vries, A., Pan, B., Brunet, L., Hunt, J., Paton, J., van Kampen, E., Knight, D., Evans, A., Rook, G., & Lightman, S. (2007). Identification of an immune-responsive mesolimbocortical serotonergic system: Potential role in regulation of emotional behavior Neuroscience, 146 (2), 756-772 DOI: 10.1016/j.neuroscience.2007.01.067