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Social skill in a pill?

June 9, 2011 19 comments

As we learn more about the unique behaviors of different animal species and how circuits in the brain control those behaviors, we will come upon more options for treating brain-based disorders.  In the case of autism spectrum disorders, a surprising potential treatment for social challenges emerged from the little-known prairie vole. The new research was published in April online in Biological Psychiatry and supported by Autism Speaks.

Prairie voles may resemble pet store hamsters, but their ordinary appearance obscures unique behavior.  These voles are among the 5% of all mammals that are monogamous—that is they form a mating pair that remains for the life of the animal.  Contrast this seemingly virtuous performance with a similar species—the meadow vole—that engages a much more promiscuous mating strategy.  For each animal, the chosen mating strategy makes sense in terms of available mating partners and other environmental pressures. However, these mating strategies also produce consequences in terms of the animal’s “social skills” and the neural circuits which serve these behaviors.

Prairie vole females, who mate for life, are relatively picky.  So, when introduced to a new male, not surprisingly, female prairie voles tend to a be careful—wanting more than just a single visit before choosing her mate. This situation affords researchers an opportunity that Larry Young, Ph.D. at Emory University exploits in the partner preference task.

The partner preference task enabled researchers to dissect the social learning that occurs in voles soon after meeting.  A female prairie vole is paired with a male for up to 24 hours so they can meet, but not mate.  During this time, researchers can give the voles different drug compounds to manipulate this first date in various ways.  From the sensory cues, to the rewarding squirts of neurotransmitter, Dr. Young and his colleagues are learning the essential ingredients for effective social learning.

The first essential ingredient is oxytocin.  This well-studied hormone is involved in birth and lactation and has more recently been shown to enhance the much more subtle social perception of trust in humans. Oxytocin administration has also been shown to increase the amount of gaze to the eye region of a face in individuals with autism.

Pair bonding in the prairie vole requires oxytocin.  The brain regions that bind this hormone are closely associated with areas of the brain that signal reward and the “reward neurotransmitter”, dopamine.  In fact, if the brain binding sites for dopamine are blocked by a competing chemical, pair bonds between prairie voles do not form.  This result reveals that the reward system must actively participate for these strong social bonds to form.

Recall the very similar-looking but very differently behaving vole called the meadow vole.  What creates their very different patterns of social engagement in these two species?  Dr. Young and colleagues showed that the distribution of receptors for the hormone oxytocin was a primary difference between the two species of animals.  In fact, female meadow voles that were made to express oxytocin receptors in a prairie vole pattern began behaving just like prairie voles with regard to mating behavior.  The promiscuous voles became monogamous by changing the expression of receptors in the brain.

This background would seem to be an elaborate set up to discuss the drug that makes the difference, but the value that these animals bring to research can not be underestimated.   The overt differences in behavior led to the discovery of hidden differences in brain physiology, which can be manipulated using drugs to improve the lives of humans.

Using a compound called d-cycloserine (DCS) the research team was able to enhance the cognitive processes involved in developing a partner preference in prairie voles. The changes are likely due to two factors:  1) an enhancement of the sensory cues that accompany a social interaction, which are primarily smell-based for rodents.  2) a boost of the memory of the social interaction, so that the partner will be recognized and associated with a positive encounter when they next meet.  The dose of DCS matters as only a low dose—one that increases glutamate neurotransmission—elicits a bias for choosing the previously met partner over the stranger.  Higher doses of DCS have a different effect on the receptor causing an overall reduction in glutamate transmission and providing no bias in the partner preference task.

What is the relevance of this to autism?  Imagine if one were able to enhance the interest of social stimuli prior to a therapy session.  Could the sort of compounds Dr. Young and his colleagues are investigating be beneficial when used in addition to behavioral therapy for helping individuals on the spectrum focus develop healthy patterns of social engagement?  In an preliminary study published in 2004 by a different group of researchers, DCS decreased social withdrawal in individuals with ASD as measured by the Aberrant Behavior Checklist.  Dr. Young and colleagues continue their research with DCS and other compounds that improve the salience of social features of an environment.  We look forward to seeing more of these results translate into meaningful treatments for people as this research direction progresses.

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