'Love hormone's role in social interaction wider than we believed

Oxytocin, often referred to as "the love hormone," is involved in a broader range of social interactions than previously understood, according to a study.

The Stanford University School of Medicine discovery may have implications for neurological disorders such as autism, as well as for scientific conceptions of our evolutionary heritage.

Scientists estimate that the advent of social living preceded the emergence of pair living by 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.

The new study pinpoints a unique way in which oxytocin alters activity in a part of the brain that is crucial to experiencing the pleasant sensation neuroscientists call "reward." 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.

"People with autism-spectrum disorders may not experience the normal reward the rest of us all get from being with our friends," said senior author Robert Malenka. "For them, social interactions can be downright painful. So we asked, what in the brain makes you enjoy hanging out with your buddies?"

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.

For this study, Malenka and lead author Gül Dolen 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 its centrality to the reward system.

In an extensive series of sophisticated, highly technical experiments, Dolen, Malenka and their teammates located the oxytocin receptors in the murine nucleus accumbens. These receptors lie not on nucleus accumbens nerve cells that carry signals forward to numerous other reward-system nodes 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 another important substance, serotonin, triggering changes in nucleus accumbens activity. In fact, popular antidepressants such as Prozac, Paxil and Zoloft belong to a class of drugs called serotonin-reuptake inhibitors that increase available amounts of serotonin in brain regions, including the nucleus accumbens.

As the Stanford team found, oxytocin acting at the nucleus accumbens wasn't simply squirted into general circulation, as hormones typically are, but was secreted at this spot by another nerve tract originating in the hypothalamus, a multifunction midbrain structure. Oxytocin released by this tract binds to receptors on the dorsal Raphe projections to the nucleus accumbens, in turn liberating serotonin in this key node of the brain's reward circuitry. The serotonin causes changes in the activity of yet other nerve tracts terminating at the nucleus accumbens, ultimately resulting in altered nucleus accumbens activity - and a happy feeling.

"There are at least 14 different subtypes of serotonin receptor," said Dolen. "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."

Malenka and Dolen said they think 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.

The study appears in the journal Nature.