Neurobiology of Anabolic-Androgenic Steroid Abuse

Abstract

Anabolic-androgenic steroids (AAS) are both performance-enhancing substances and drugs of abuse. Although AAS are banned in competitive sports, they are widely used by both elite and rank-and-file athletes. All AAS are derived from testosterone, the principle endogenous androgen produced by the testes of adult men. While AAS increase muscular strength and athletic performance, they also have serious consequences for health and behavior. AAS are implicated in maladaptive behavioral and cognitive changes such as increased risk-taking and altered decision-making. However, effects of AAS on cognition are not well understood. Studies of human AAS users are limited by an inability to control for pre-existing psychopathology and behavioral differences. Furthermore, in order to understand AAS effects on behavior, it is important to discover how AAS impact the brain. Animal models of AAS abuse parallel human studies to uncover effects on cognition, decision-making, and underlying neurobiological mechanisms. In operant discounting tests, rats treated with chronic high-dose testosterone are less sensitive to effort, punishment, and delay but are more sensitive to uncertainty. Likewise, they demonstrate impaired cognitive flexibility when tested for set-shifting and reversal learning. It appears that AAS induce many of these cognitive changes via effects on the mesocorticolimbic dopamine system, particularly through the dopamine D1- and D2-like receptors in subnuclei of the nucleus accumbens. AAS also have rewarding effects mediated by similar neural circuits. In preclinical studies, animals will voluntarily self-administer AAS. Human users may develop dependence. These findings highlight the vulnerability of brain circuits controlling cognition and reward to androgens at high doses.