Wednesday, February 21, 2018

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.

Wednesday, February 14, 2018

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.

Tuesday, February 6, 2018

Addicted to Love

Image from imagerymajestic at
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.

Tuesday, January 30, 2018

Freezing the Winter Away

An edited reposting of an article from January 8, 2014.

During this frigid winter we can be thankful for our home heating, our layers of warm clothing, and most of all, our bodies’ abilities to generate heat. But it is times like these that make me wonder about our friends that live outside year-round… especially those that don’t generate most of their own body heat. How do they survive these periods of intense cold? There are several species of North American frogs that have an unusual trick up their sleeve: They freeze nearly solid and still live to see the next spring.

This picture of a wood frog is by Ontley at Wikimedia Commons.
Frogs are ectothermic, meaning they take on the temperature of their surroundings rather than generate their own body heat. This introduces some intriguing questions about how these species even exist in northern climates that experience freezing temperatures every year. When various North American frog species (including wood frogs, spring peepers, western chorus frogs, and a few gray tree frog species) take on freezing winter temperatures, they actually allow their bodies to freeze nearly solid. For most species, this would be a deadly approach: a frozen circulatory system would halt the delivery of oxygen to cells, which require oxygen to generate the energy they need to do just about everything a cell does. Furthermore, jagged ice crystal edges could rupture the cells they are inside. Dead cells lead to dead organs, which in turn lead to dead animals. These freezing frogs have found the secrets to freezing without killing their cells.

The first secret of the freezing frogs is to spend the winter snuggled in the leaf litter below the snow. This environment insulates and protects the frogs from the deadly wind chills we have been facing for the last several days.

The second secret of the freezing frogs is a creative use of colligative properties. Colligative properties are properties of solutions that depend on the ratio of the number of liquid molecules to the number of molecules of stuff dissolved in that liquid. One of those properties is called freezing point depression: The temperature at which a liquid will freeze can be lowered by adding particles to it. (This is why salt is spread on roads in the winter). A critical component of the freezing frog strategy is for the liver to produce massive amounts of glucose in response to the start of freezing. This glucose is pumped throughout the body, which lowers the freezing point of all of the organs.

A third secret of the freezing frogs is the use of ice nucleating agents: proteins that actually encourage freezing. This may seem counterintuitive, but remember that ice crystals inside cells can cause them physical damage. By having a high concentration of ice nucleating agents in the fluid between the cells, this ensures that ice first forms in the spaces surrounding the cells. When ice forms, the ice crystals are made of only water molecules, which draws water out of the solution and leaves behind a higher concentration of other stuff (like glucose) in between the cells. The high concentration of glucose between the cells draws water out of the cells and into that space. This additional water also freezes. In the end, the cells are chock-full of particles, lowering their freezing temperature, and are surrounded by ice, which insulates the cells. Thus, this process of ice formation around the cells prevents ice from forming inside the cells.

A fourth secret of the freezing frogs is a metabolic shift. Most animal cells rely on oxygen to produce the energy they need to support their demands. But cells have ways of producing energy without oxygen too. These ways are not very efficient, but are useful when there is not enough oxygen available to meet demand (such as when a seal dives or a cheetah reaches burst speed). When freezing frogs start to freeze and oxygen delivery to the cells slows and eventually stops, their cells shift from an oxygen-reliant system of energy creation to an oxygen-independent system of energy creation. Additionally, freezing organs do less and don’t require as much energy anyway, so they can continue functioning at low levels for a long time if the freezing spell is prolonged.

When the environment warms up (as forecasters promise will happen), the body temperatures of these frogs raise and body fluids slowly become liquid again. The heart starts to beat again within hours of the start of thawing and oxygen can again be delivered around the body. The delivery of oxygen-carrying blood helps the rest of the organs return to their normal functions.

There are still many secrets of these freezing frogs left to uncover. Maybe you’ll be the one to do it… once we thaw out a bit.

Want to know more? Check these out:

1. Storey, K.B. (2004). Strategies for exploration of freeze responsive gene expression: advances in vertebrate freeze tolerance Cryobiology, 48, 134-145 DOI: 10.1016/j.cryobiol.2003.10.008

2. Layne, J.R., & Lee, R.E. (1995). Adaptations of frogs to survive freezing Climate Research, 5, 53-59 DOI: 10.3354/cr005053

Tuesday, January 23, 2018

Body Clocks: What They Are and How They Work

Lately, with the new year, the #TimesUp movement, awaiting Disney’s movie A Wrinkle in Time based on one of my favorite childhood book series, and just watching my children grow faster than I thought possible, I have been thinking a lot about time. The continuous march forward, the constant rotation of the planet, and the revolution of the Earth around a distant star in its determined path all have far-reaching effects on our physiology and behavior. Our biological clocks affect everything from our sleep-wake cycles to our fertility to our mental and physical health. And it’s not just us that have them: Every living thing on Earth, including bacteria, protists, fungi, plants and animals, has them. But what do they do and how do they work?

A sleepy ferret minds his biological rhythms. Photo by Kimberly Tamkun at Wikimedia Commons.

Generally speaking, a biological clock is an organism’s inborn way of regulating its functions with respect to time. Many of these biological clocks follow circadian rhythms (changes that follow a 24-hour cycle). Vast portions of our planet have been exposed to dramatic but mostly predictable environmental changes on a 24-hour cycle since long before life existed, so it makes sense that us lifeforms have developed a means to make the best of those changes: sleeping when food is less available, having higher metabolisms when we are active, being more alert during times we are most likely to be interacting with the world.

Diagram of a human circadian rhythm by YassineMrabet at Wikimedia Commons.

Melatonin is a hormone widely known to synchronize circadian rhythms in vertebrates (animals with backbones) to the light-dark cycle of the day and night (or to an indoor room with a light timer). Melatonin is produced in response to darkness, and the longer the night, the more melatonin is produced. Rising and falling melatonin levels help determine sleep-wake cycles in animals. In animals that breed seasonally, the changing peaks of melatonin levels that correspond with dark nights getting longer or shorter stimulate the reproductive system to help synchronize breeding physiology and behavior with the seasons. Although we have known about melatonin and its effects for nearly a hundred years, we are now learning that it seems that all organisms, including bacteria, protists, fungi, plants and animals, make it. Whether it has the same effect in all organisms is yet to be determined.

In vertebrates, melatonin is produced by the pineal gland, a small structure in the center of the brain. In birds, reptiles, amphibians and fish, the pineal gland has light-sensitive cells that receive light as it passes directly through the skull and the brain! In mammals, the pineal gland receives a light signal through a more complicated pathway: Light is detected by light sensitive cells in the retinas of the eyes. They send this signal to the suprachiasmatic nucleus (SCN) in the brain, which relays it to other brain areas and then to the pineal gland. The SCN in mammals is commonly called “the master clock” due to its important role in synchronizing body rhythms with light cues.

Diagram of the human brain and the SCN by the
National Institute of General Medical Sciences at Wikimedia Commons.

Body rhythms are determined at the cellular level through the interaction of a small number of genes called clock genes. Clock genes have been found in every animal, plant and fungus studied so far. Originally, it was thought that in mammals, clock genes would only be found in the SCN. However, it now looks like clock genes are active in all cells and the SCN functions more like an orchestra conductor synchronizing the rhythms of the organs throughout the body.

Many clock genes have been discovered, and they all seem to work based on similar processes. Just last year, scientists Jeffrey Hall, Michael Rosbash, and Michael Young, were awarded the 2017 Nobel Prize in medicine for their research on clock genes in fruitflies. They found that biological clocks are self-regulated within the cell: Morning sunlight turns on a gene called the PERIOD gene, which starts to produce a protein called the Period protein. As long as there is light, Period protein accumulates to higher and higher levels. Another protein, named Timeless, shuttles Period proteins into the nucleus, where the DNA lives. The Period proteins shut down the activity of the PERIOD gene, while a third protein, called Doubletime, regulates the destruction of the excess Period proteins. The result of this process is that by nightfall, Period proteins have disappeared and sunlight is needed to start the cycle anew. This work by Hall, Rosbash and Young inspired a whole new field of molecular biology of circadian rhythms.

We have a lot more to learn about biological clocks and circadian rhythms, but what we do know is that their effects are wide-ranging. Whacky circadian rhythms have been implicated in sleep disorders, depression, bipolar disorder, cancer, obesity, and diabetes. And what else will we learn about them? Only time will tell.