NEURAL AND BEHAVIORAL ACTIONS OF ANABOLIC STEROIDS

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The long-term objective of this project is to elucidate the neural and behavioral actions of anabolic-androgenic steroids (AAS). AAS are synthetic androgen-like compounds which are taken in massive quantities by athletes with the intention of enhancing their muscular appearance, strength, and/or athletic performance. Abuse of AAS has become a major substance abuse problem in this country. AAS have been shown to have profound adverse effects on the liver, cardiovascular and endocrine systems. AAS are also known to produce severe and deleterious changes in affect and behavior, however, at the present time, few systematic studies have evaluated AAS effects on the central nervous system or behavior. Although endogenous steroid hormones (e.g., testosterone) are known to regulate sexual behavior and aggression, there is paucity of data on the neuroendocrine effects of AAS. Nonetheless, case reports clearly indicate the need for this knowledge, as alterations in reproductive function and an increase in violent behavior have been associated with AAS use. The goal of the present proposal is to investigate the effects of AAS on the central nervous system focusing on three specific questions. First, how do AAS influence sexual behavior and neuroendocrine function in adult male and female rats? Second, what is the impact of AAS on the display of aggression in adult male rats? A focus of this research proposal is to examine the effects of AAS on sexual behavior, neuroendocrine function and aggression in both gonadectomized and gonadally intact animals. Studies of AAS action in the gonadectomized rat allow for the determination of AAS actions in the absence of gonadal secretions, while analyses of AAS effects in the gonadally intact animal more closely mimic the human condition and permit evaluation of the interactions between AAS and endogenous hormones. The third goal of the proposed research is to determine the neural steroid receptors and brain areas at which AAS act in the brain using several strategies. First, the ability of AAS to compete with brain androgen, estrogen and corticosteroid receptors will be assessed. In addition, the extent to which AAS occupy cell nuclear receptors will be explored. Finally, changes in steroid receptor number which occur within specific brain areas as a consequence of chronic AAS will be examined. In all studies, special attention will be given to analyzing the effects of specific classes of AAS which are commonly abused, and comparing the behavioral and biochemical responses to different doses, dosing regimens, and durations of exposure to these drugs. Taken together, the results from these experiments will lead to a better understanding of the impact of AAS on human health and behavior.