NEUROPEPTIDE BASIS OF SOCIAL LOSS AND DEPRESSION

Emory University, Atlanta GA

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We have demonstated that variation in early life social stimuli has a long term impact on later life social behaviors as well as neuropeptide systems in the brain. To vary early life social experience, we raised prairie vole pups in family units consisting of a mother and father (biparental) or mother only. We found that prairie vole females reared by single mother displayed significantly less alloparental behavior than females raised by both parents. Furthermore, both males and females raised by single parents were significantly less likely to form a partner preference than those raised by both parents. We also examined several neuropeptide systems in the brain and discovered that family structure significantly altered the number of oxytocin neurons in the hypothalamus as well as CRF2 receptor densities. Specifically, prairie voles raised by single mothers had more oxytocin expressing neurons in the hypothalamus than those raised by both parents. Overall, these studies demonstrate that early life nurturing experience can impact the neurobiological mechanisms that regulate adult relationship formation in adults. Our initial publication from this grant demonstrated that the CRF system mediates the increase in depressive like behavior following the loss of a bonded partner (Bosch et al., Neuropsychopharmacology, 2009). In an effort to determine the neuroanatomical site of action of CRF we have been using immunocytochemistry to determine the location of CRF receptor containing neurons in the prairie vole brain. This has led to the very exciting discovery that the CRF2 receptor is virtually completely co-localized with oxytocin. In addition to being co-localized in the cell bodies of the hypothalamus, CRF2 receptors are located on oxytocin fibers in the nucleus accumbens, which we know are involved in regulating social behaivors. This suggests that CRF2 receptor may play a major role in the regulation of oxytocin secretion.