Women have been excluded or underrepresented in much past research examining alcohol use and dependence. Yet, the research available has found women to differ from men in their alcohol drinking patterns and their sensitivity to various consequences of ethanol. These sex differences begin to emerge during adolescence and become more pronounced at maturity. While social, cultural and environmental influences undoubtedly contribute to the emergence of sex differences in alcohol intake and effects, biological factors also are likely to play an important role. Yet, despite the marked hormonal and neural changes associated with puberty and the other physiological transitions of adolescence, little is known of how these factors might contribute to the ontogeny of sex differences in ethanol intake and sensitivity. Determining the role of pubertal increases in gonadal hormones on the emergence of sex differences in alcohol consumption and consequences is ethically challenging in humans, but can be approached using animal models that share with human adolescents certain basic age-typical similarities in hormonal, neural, and behavioral characteristics. The proposed work will use a simple animal model of adolescence in the rat to examine the role of pubertal increases in gonadal hormones in both males and females on the emergence of sex differences in ethanol intake and consequences. Given mounting evidence that pubertal rises in gonadal steroids can exert organizational effects on the brain to support the differentiation of certain sex-typical behaviors at puberty, both organizational as well as activational (direct hormone-stimulated) effects of gonadal hormones will be explored. This will be accomplished via gonadectomizing animals either pre-pubertally or in adulthood, and hormone replacement beginning either at puberty or maturity. Focusing on alcohol-related sex differences that begin to emerge during the adolescent period and become marked in adulthood, the proposed studies will assess both organizational and activational effects of the rise in gonadal hormones at puberty on expression of sex differences in ethanol intake, ethanol sensitivity (indexed by ethanol-induced social suppression) and ethanol stress interactions. Despite the increasing emphasis on alcoholism as a developmental disorder, little is known of the potential role of the rise in pubertal hormones in promoting the emergence of sex-typical patterns of alcohol use, consequences and abuse. The proposed work will address this considerable gap in our understanding, data that should help inform the development of sex-relevant strategies for prevention, identification, and treatment of alcohol use disorders among youth and young adults.
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