CNS Estrogen Receptors and Social Behavior

University Of Illinois At Chicago, Chicago IL

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Abstract

DESCRIPTION (provided by applicant): Recombinant adeno-associated viral (rAAV) vectors can be used to directly introduce genes into cells making local manipulation of receptors possible and site-specifically alter the sensitivity of an animal to hormones. The goal of this study is to use this developing technology to enhance ERalpha in male prairie voles (Microtus ochrogaster). E influences a variety of male and female behaviors, including aggression, affiliation, social preferences, parental behavior, and mating. Prairie voles provide a unique opportunity to use rAAV to understand the role of steroids in regulating social behavior. Foremost, prairie voles are highly social and monogamous, displaying many social interactions similar to humans, making them a better rodent model for studying social behavior than species such as rats and mice. The development of ER knockout (KO) mice (a and a) has provided significant insight into the actions of E and with the advent of rAAV ER can be replaced in specific areas providing a powerful tool for examining the effects of E. A disadvantage of ERKO mice is they not only lack ER as adults, but also are not exposed to the organizational effects of E during development. In contrast prairie voles are subject to the developmental effects of E, but at the same time, males, at least from Illinois, express little or no ERalpha, and significantly less than females, in the BST and the MeA. In rats and mice, where male/female social interactions are often limited to mating, both males and females express high levels of ERalpha in the MeA and BST. The MeA and BST play a major role in regulating social behavior, and a comparison of the pattern found in prairie voles with rats and mice suggests that the lack of ERalpha in these areas could account for increased social behavior displayed by male prairie voles. This possibility is further supported by comparing social behavior and ERalpha between prairie voles from Illinois (IL), which are monogamous, and Kansas (KN), which are less social and show many polygynous characteristics. KN males display an ERalpha pattern intermediate to IL prairie voles and rats, with KN males expressing significantly more ERalpha in the BST and the MA than IL males, but less than KN females in the BST. IL male prairie voles will be transfected with rAAV-ERalpha in the BST and MeA and transfected, sham and control males will be tested for aggression, parental behavior, partner preference, social contact (same and opposite sex), and sexual behavior, with the prediction being that increasing ERalpha will decrease affiliation and increase aggression.