The social avoidance that normally develops when a mouse repeatedly experiences defeat by a dominant animal disappears when it lacks a gene for a memory molecule in a brain circuit for social learning, scientists funded by the National Institutes of Health's (NIH) National Institute of Mental Health (NIMH) have discovered. Mice engineered to lack this memory molecule continued to welcome strangers in spite of repeated social defeat. Their unaltered peers subjected to the same hard knocks became confirmed loners — unless the researchers treated them with antidepressants.
“For both mice and men, social status is important; for mice, losing to a dominant mouse usually means that they avoid the dominant and they avoid social situations,” explained NIMH director Dr. Thomas Insel. “These new findings add to a growing literature on the molecular basis of social behavior, helping us to know where as well as how social information is encoded in the brain.”
The results reveal neural mechanisms by which social learning is shaped by psychosocial experience and how antidepressants act in this particular brain circuit. They also suggest new strategies for treating mood disorders such as depression, social phobia and post-traumatic stress disorder, in which social withdrawal is a prominent symptom. Drs. Olivier Berton and Eric Nestler, University of Texas Southwestern Medical Center (UTSMC), and colleagues, report on their study in the February 10, 2005 issue of Science.
Coursing from a hub in the center of the brain (ventral tegmental area), the relevant circuit mediates responses to emotionally important environmental stimuli via release of dopamine. Activity of this neurotransmitter is regulated in the circuit by brain derived neurotrophic factor (BDNF), which is known to play a key role in memory (http://www.nimh.nih.gov/Press/prbdnf.cfm ). Berton, Nestler and colleagues suspected that BDNF plays a similarly pivotal role in social learning.
The researchers say the study “suggests new directions for antidepressant drug discovery.”
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