Grant Abstract: Anabolic Androgenic Steroid Effects on Brain & Behavior

Grant Number: 5R01DA010886-06
PI Name: Marilyn McGinnis
Project Title: Anabolic Androgenic Steroid Effects on Brain & Behavior

Abstract: DESCRIPTION (provided by applicant): The overall goal of this research is to understand the impact of peripubertal AAS abuse on sociosexual and reproductive maturation. This is an important area of AAS research in view of recent data indicating that AAS abuse has risen in teenagers. Critical hormonal and neurological changes occur during puberty which are responsible for the development and expression of aggressive, sexual and sociosexual behaviors. As human studies often rely on subjective reports, a rat model is used to study AAS effects on behavior. The aims of this project are to assess the behavioral and neuroendocrine consequences of AAS abuse in pubertal rats. Our work has focused on the individual effects of three commonly abused AAS, testosterone (TP), nandrolone (ND) and stanozolol (ST). In adults we found that TP stimulates aggression, and a phase advance in circadian rhythms. In contrast, ST suppresses aggression and sexual behavior. Because ST is not aromatizable, Aim 1 will determine whether the suppressive effect of ST on aggressive and reproductive behaviors is due to lack of estrogenic exposure. The results of this study will also demonstrate whether estrogen is required for development of sociosexual and aggressive behaviors in pubertal males. Aim 2 will assess whether the behavioral changes resulting from peripubertal AAS abuse are reversible. Since AAS users typically "stack" (combine) AAS, Aim 3 will determine whether 'stacking' ameliorates or exaggerates AAS effects on aggression and reproductive behavior. We previously found that TP induces an exaggerated response to physical provocation even toward non-threatening opponents. Aim 4 will examine whether this phenomenon extends to aggression toward females. Aim 5 will investigate whether serotonin plays a role in mediating AAS effects on aggression to delineate possible mechanisms underlying AAS effects on brain in juveniles. The fact that dynamic hormonal changes occur during puberty, and the brain is affected by these hormonal influences, emphasizes the need for more research on the effects of AAS exposure during adolescence.

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