Love Hormone May Play Role In Autism

Sep 12 2013

Scientists at the Stanford University School of Medicine say a study with mice has demonstrated that oxytocin, aka the "love hormone," appears to be involved in a wider range of social activities than previously thought.

They also believe that their discovery ("Social reward requires coordinated activity of nucleus accumbens oxytocin and serotonin"), published today in Nature, has implications for neurological disorders such as autism and for insights on the evolutionary history of Homo sapiens.

Oxytocin is the focus of much interest for its apparent roles in establishing trust between people. It has also been administered to children with autism spectrum disorders in clinical trials. Oxytocin has been branded with the "love hormone" handle because of its importance in the formation and maintenance of strong mother-child and sexual attachments.

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

"[Our] results demonstrate that the rewarding properties of social interaction in mice require the coordinated activity of oxytocin and 5-HT [5-hydroxytryptamine] in the nucleus accumbens, a mechanistic insight with implications for understanding the pathogenesis of social dysfunction in neuropsychiatric disorders such as autism," wrote the investigators in the Nature article.

In addition, the Stanford team maintains that its 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 Robert Malenka, M.D., Ph.D., 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?"

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 are associated with increased autism risk.

In the 1970s, biologists learned that in prairie voles, which mate for life, the nucleus accumbens, which is involved in the brain's reward system, is replete with oxytocin receptors. Disrupting the binding of oxytocin to these receptors impaired prairie voles' monogamous behavior. In many other species that are not monogamous by nature, such as mountain voles and common mice, the nucleus accumbens appeared to lack those receptors.

For the current study, Dr. Malenka's group focused on untangling the complicated neurophysiological underpinnings of oxytocin's role in social interactions. They zeroed in on biochemical events taking place in the nucleus accumbens.

"Although the nucleus accumbens receives oxytocin receptor-containing inputs from several brain regions, genetic deletion of these receptors specifically from dorsal raphe nucleus, which provides serotonergic [5-HT] innervation to the nucleus accumbens, abolishes the reinforcing properties of social interaction," continued the scientists in their Nature article. "Furthermore, oxytocin-induced synaptic plasticity requires activation of nucleus accumbens 5-HT1B receptors, the blockade of which prevents social reward."

"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," explained Gül Dölen, M.D., Ph.D., a postdoctoral scholar in Dr. Malenka's group. "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."

The new discovery shows that mice do indeed have oxytocin receptors at a key location in the nucleus accumbens and, importantly, that blocking oxytocin's activity there significantly diminishes these animals' appetite for socializing.

Drs. Malenka and Dölen think their findings in mice can be generalized to humans because the brain's reward circuitry has been 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.

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