title: Some rewarding effects of androgens may be mediated by actions of its 5alpha-reduced metabolite 3alpha-androstanediol.
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 gamma-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.
authors.affiliation: Department of Psychology, Centers for Neuroscience and Life Sciences Research Building, Room 1058, The University at Albany-State University of New York, 1400 Washington Avenue, Albany, NY 12222, USA. cafrye@albany.edu
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Frye
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism*; D000293:Adolescent; D045930:Anabolic Agents / Q000494:pharmacology*; D000728:Androgens / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology* / Q000502:physiology; D015113:Androstane-3,17-diol / Q000494:pharmacology*; D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects; D004298:Dopamine / Q000502:physiology; D004361:Drug Tolerance; D006801:Humans; D009638:Norepinephrine / Q000502:physiology; D012201:Reward; D013375:Substance Withdrawal Syndrome / Q000523:psychology; D019966:Substance-Related Disorders / Q000523:psychology
chemical_list: D045930:Anabolic Agents; D000728:Androgens; D015113:Androstane-3,17-diol; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; D004298:Dopamine; D009638:Norepinephrine