Anabolic steroid addiction? Insights from animal studies
Androgenic-anabolic steroids (AAS) are drugs of abuse. They are taken in large quantities by athletes and others to increase performance, with negative long-term health consequences. Although AAS were banned from Olympic competition in 1975, steroid abuse continues. However, the potential for reinforcement and dependence on AAS has received relatively little attention. In particular, it is difficult in humans to separate the direct psychoactive effects of AAS from reinforcement due to their systemic anabolic effects. Recent studies in rats and hamsters have demonstrated that testosterone is reinforcing using conditioned place preference and self-administration. In particular, our laboratory has provided evidence of voluntary testosterone intake, including oral, intravenous, and intracerebroventricular (icv) self-administration. Male and female Syrian hamsters self-administer testosterone, dihydrotestosterone, nandrolone decanoate, or drostanolone icv across a range of concentrations (0.1 -2.0 ug/ul). The antiandrogen flutamide blocks testosterone self-administration, suggesting that androgen receptors (AR) are required for reinforcement. However, this effect may not depend on classical genomic AR, since male rats with a mutation in the genomic AR also self-administer androgens. Instead, it is likely that the reinforcing effects of androgens are mediated by non-genomic AR. When taken in large doses (>40 ug in 4h), testosterone icv produces torpor and, occasionally, death. Symptoms of androgen overdose resemble those of opioid intoxication, and androgen withdrawal can be induced by the opioid antagonists naloxone and naltrexone. However, with continued exposure, hamsters develop tolerance to the depressive effects of testosterone. Tolerance and withdrawal are key criteria for addiction. Thus, it appears that AAS may be addictive, even in an experimental context where athletic performance is irrelevant. (Supported by NIH DA-12843).