In a breakthrough study from Stanford University School of Medicine, researchers have shown that oxytocin — known as the “love hormone” because of its important role in the formation and maintenance of mother-child bonding and sexual attachments — is actually involved in a much broader range of social connections. The researchers discovered that oxytocin released through any type of social connectivity triggered the release of serotonin. In a chain reaction, the serotonin then activated the ‘reward circuitry’ of the nucleus accumbens resulting in a happy feeling.
This new discovery offers clues to our evolutionary psychology and has promising applications for treatments of neurological disorders such as autism. The study titled, “Social Reward Requires Coordinated Activity of Nucleus Accumbens Oxytocin and Serotonin” appears in the September 12, 2013 issue of Nature.
For this study, Malenka and lead author Gül Dölen, MD, PhD, a postdoctoral scholar in his group with over 10 years of autism-research expertise, teamed up to untangle the complicated neurophysiological underpinnings of oxytocin's role in social interactions. They focused on biochemical events taking place in a brain region called the nucleus accumbens, known for being central to our reward system.
The Stanford study suggests that one-on-one pair bonding probably evolved from the human affinity for living collectively in a group. Many other studies have found that social isolation is detrimental for our well-being. One of the problems of modern living in a Facebook age is that many of us feel isolated because our social network exists in cyberspace which causes our biology to short-circuit.
As hunter-gatherers, early humans traveled in small bands and lived in groups. It is believed that group living preceded the emergence of living as a pair by about 35 million years. The new study suggests that oxytocin's role in one-on-one bonding probably evolved from an existing, broader affinity for group living.
Oxytocin and the Human Urge to Tend-and-Befriend
In the 1970s, biologists learned that in prairie voles, which mate for life, the nucleus accumbens is packed full of oxytocin receptors. Blocking oxytocin receptors disrupted the prairie voles' monogamous behavior. In species that are not biologically wired to be monogamous, such as mountain voles and common mice, the nucleus accumbens doesn’t have oxytocin receptors.
"From this observation sprang a dogma that pair bonding is a special type of social behavior tied to the presence of oxytocin receptors in the nucleus accumbens. But what's driving the more common group behaviors that all mammals engage in – cooperation, altruism or just playing around – remained mysterious, since these oxytocin receptors were supposedly absent in the nucleus accumbens of most social animals," said Dölen.
The new discovery shows that mice need to have oxytocin receptors at a very specific location in the nucleus accumbens and, importantly, that blocking oxytocin's activity there significantly diminished these animals' appetite for any type of socializing. Dölen, Malenka and their Stanford colleagues have identified – for the first time – the specific nerve tract that secretes oxytocin in the region, and were able to pinpoint the effects of oxytocin release on other nerve tracts projecting to this area.
Malenka points out, “Mice can squeak, but they can't talk. You can't ask a mouse, 'Hey, did hanging out with your buddies a while ago make you happier?" So, to explore the social-interaction effects of oxytocin activity in the nucleus accumbens, the investigators used a standard measure called the conditioned place preference test.
"It's very simple," Malenka said. "You like to hang out in places where you had fun, and avoid places where you didn't. We give the mice a 'house' made of two rooms separated by a door they can walk through at any time. But first, we let them spend 24 hours in one room with their littermates, followed by 24 hours in the other room all by themselves. On the third day we put the two rooms together to make the house, give them complete freedom to go back and forth through the door and log the amount of time they spend in each room."
Like humans, mice prefer to spend time in a space that reminds them of having fun and feeling good. The companionship of other mice was key to making the mice feel good. But the urge to have a social connection with other mice vanished when oxytocin activity in their nucleus accumbens was blocked.
Oxytocin Triggers the Release of Serotonin
Oxytocin alters activity in a part of the brain that creates makes us feel good hence the ideas it being a ‘reward center.’ Malenka, who is a professor in psychiatry and behavioral sciences, has spent the past two decades studying the reward system.
He describes this as “a network of interconnected brain regions responsible for our sensation of pleasure in response to a variety of activities such as finding or eating food when we're hungry, sleeping when we're tired, having sex or acquiring a mate, or, in a pathological twist, taking addictive drugs. The reward system has evolved to reinforce behaviors that promote our survival.”
In an extensive series of sophisticated, highly technical experiments, Malenka and his teammates located the oxytocin receptors in a part of the brain called the murine nucleus accumbens. These receptors do not lie on actual nucleus accumbens nerve cells but, instead, at the tips of nerve cells forming a tract from a brain region called the dorsal Raphe, which projects to the nucleus accumbens.
The dorsal Raphe secretes serotonin, which triggered changes in nucleus accumbens activity which carry signals forward to numerous other reward-system nodes. Antidepressants such as Prozac, Paxil and Zoloft belong to a class of drugs called serotonin-reuptake inhibitors (SSRIs) that increase available amounts of serotonin in brain regions, including the nucleus accumbens.
The Stanford team discovered that unlike most hormones, oxytocin wasn't 'squirted’ into general circulation but was secreted directly to a spot on the nucleus accumbens via a nerve tract originating in the hypothalamus, which is a multifunctional midbrain structure.
Oxytocin binds to receptors on the dorsal Raphe projections to the nucleus accumbens, in turn freeing up serotonin in this key node of the brain's reward circuitry. In a neurobiological chain reaction, the serotonin causes changes in the activity of yet other nerve tracts terminating at the nucleus accumbens. This cascade of hormones and neurotransmitters ultimately results in altered nucleus accumbens activity and makes you feel happy.
"There are at least 14 different subtypes of serotonin receptor," said Dölen. "We've identified one in particular as being important for social reward. Drugs that selectively act on this receptor aren't clinically available yet, but our study may encourage researchers to start looking at drugs that target it for the treatment of diseases such as autism, where social interactions are impaired."
Oxytocin and Autism-Spectrum Disorder
Oxytocin has been the focus of intense scrutiny for its apparent roles in establishing trust between people. There has been some controversy about administering oxytocin to children with autism spectrum disorders in clinical trials. "People with autism-spectrum disorders may not experience the normal reward the rest of us all get from being with our friends," said Robert Malenka, MD, PhD, the study's senior author. "For them, social interactions can be downright painful. So we asked, what in the brain makes you enjoy hanging out with your buddies?"
The findings not only provide validity for ongoing trials of oxytocin in autistic patients, but also suggest possible new treatments for neuropsychiatric conditions in which social activity is impaired.
Some genetic evidence suggests the awkward social interaction that is a hallmark of autism-spectrum disorders may be at least in part oxytocin-related. Certain variations in the gene that encodes the oxytocin receptor – a cell-surface protein that senses the substance's presence – are associated with increased autism risk.
Conclusion: Social Connectivity Is Key to Our Survival.
Malenka and Dölen believe their findings in mice are “highly likely to generalize to humans because the brain's reward circuitry has been so carefully conserved over the course of hundreds of millions of years of evolution. This extensive cross-species similarity probably stems from pleasure's absolutely essential role in reinforcing behavior likely to boost an individual's chance of survival and procreation.”
If you’d like to learn more about this topic please check out my Psychology Today blogs: "These are Revolutionary Times for the Biology of Psychology", “The Neurobiology of the “Love” Hormone Revealed”, “Neuroscientists Confirm that Our Loved Ones Become Ourselves”, “Evolution Does Not Reward Selfish and Mean People” and “Social Connectivity Drives the Engine of Well-Being.”