Effects of exogenous testosterone on the ventral striatal BOLD response during reward anticipation in healthy women

Correlational evidence in humans shows that levels of the androgen hormone testosterone are positively related to reinforcement sensitivity and competitive drive Structurally similar anabolic-androgenic steroids (AAS) are moreover widely abused, and animal studies show that rodents self-administer testosterone These observations suggest that testosterone exerts activational effects on mesolimbic dopaminergic pathways involved in incentive processing and reinforcement regulation However, there are no data on humans supporting this hypothesis We used functional magnetic resonance imaging (fMRI) to investigate the effects of testosterone administration on neural activity in terminal regions of the mesolimbic pathway In a placebo-controlled double-blind crossover design, 12 healthy women received a single sublingual administration of 5 mg of testosterone During MRI scanning, participants performed a monetary incentive delay task, which is known to elicit robust activation of the ventral striatum during reward anticipation Results show a positive main effect of testosterone on the differential response in the ventral striatum to cues signaling potential reward versus nonreward Notably, this effect interacted with levels self-reported intrinsic appetitive motivation individuals with low intrinsic appetitive motivation exhibited larger testosterone-induced increases but had smaller differential responses after placebo Thus, the present study lends support to the hypothesis that testosterone affects activity in terminal regions of the mesolimbic dopamine system but suggests that such effects may be specific to individuals with low intrinsic appetitive motivation By showing a potential mechanism underlying central reinforcement of androgen use, the present findings may moreover have implications for our understanding of the pathophysiology of AAS dependency (C) 2010 Elsevier Inc All rights reserved