Some rewarding effects of androgens may be mediated by actions of its 5α-reduced metabolite 3α-Androstanediol

Some rewarding effects of androgens may be mediated by actions of its 5α-reduced metabolite 3α-Androstanediol

Cheryl A. Frye

Pharmacol Biochem Behav.

Abstract

The abuse of anabolic androgenic steroids (AS) is a growing problem; however, the effects and mechanisms underlying their addictive effects are not well understood. Research findings regarding androgen abuse in people and hedonic effects of androgens in laboratory rats are reviewed. Androgens, like other steroids, can have traditional actions via cognate intracellular steroid receptors, as well as other substrates. Our recent results indicate that testosterone (T) metabolites may have actions in part via γ–aminobutyric acid (GABA)_A/benzodiazepine receptor complexes (GBRs) and/or dopaminergic neurons in the nucleus accumbens, to mediate T’s positive hedonic states. This may provide the basis for positive reinforcing effects of androgen seeking and use behavior. Following a comprehensive review of the background literature, our findings are presented that have explored the extent to which metabolites of T mediate euphorogenic effects of androgens by acting in the nucleus accumbens. Then results regarding whether GBRs are necessary substrates for androgens’ positive hedonic effects are discussed. Lastly, research that addresses if dopaminergic neurons in the nucleus accumbens are necessary for these effects of androgens are discussed. This review provides a comprehensive examination of the hedonic properties and abuse/addiction potential of androgens and the putative mechanisms underlying these effects.

Summary

In summary, androgen and AS use is widespread and increasing. The background literature regarding effects of AS underscore the notion that AS can have effects that are akin to that of other drugs of abuse. Use of AS is associated with adverse illicit use of other drugs of abuse, as well as physiological and behavioral consequences (including violence and aggression). Anabolic-androgenic steroids use may lead to addiction, dependence, and withdrawal such that use is often continued despite short- and long-term health risks. Understanding the pharmacological effects of AS is important, but attempts have been confounded both by the complex receptor-and non-receptor-bound actions of AS and the lack of basic understanding of androgens’ actions and their hedonic effects and neurobiological mechanisms. The research described addresses whether T, a widely used AS, has positive euphorogenic effects which may contribute to their abuse liability in part through non-genomic actions. The implications of this research are that AS and/or T may produce some of their positive hedonic effects by enhancing 3α-diol production, which in turn have actions at GBRs in the NA, which synapse on dopaminergic neurons, to produce positive hedonic effects. Further research is needed to ascertain other hedonic effects and mechanisms of androgens.

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del.icio.us Tags: steroids,testosterone,reward,reinforcement,hedonic,conditioning,GABAA receptors,dopamine receptors,anxiety,affect,learning