The nucleus accumbens as a site of action for rewarding properties of testosterone and its 5α-reduced metabolites

Testosterone (T)'s positive hedonic effects may be mediated by actions of its metabolites, dihydrotestosterone (DHT) or 3alpha-androstanediol (3alpha-diol), in the nucleus accumbens (NA). In Experiment 1, adult, intact, male rats were systemically administered 1 mg of T, DHT, 3alpha-diol or vehicle, at different time points to examine concentrations of androgens in the NA. Rats administered 3alpha-diol had significantly increased concentrations of 3alpha-diol in the region of the brain encompassing the NA. These data are consistent with previous data from our laboratory demonstrating that 3alpha-diol elicits a conditioned place preference (CPP) more effectively than either T or DHT, when administered systemically. In Experiment 2, rats received implants of T, DHT or 3alpha-diol to the NA immediately prior to placement in the CPP apparatus on conditioning days. Implants of T, DHT or 3alpha-diol, but not vehicle, significantly increased time spent on the non-preferred side of the chamber on the test day. This effect was only produced by androgenic stimulation of the shell of the NA and not the core of the NA. Thus, androgen regimens we have previously found to enhance CPP produced the greatest increases in 3alpha-diol concentrations in the NA region and direct implants of T, DHT or 3alpha-diol to the shell, but not the core, of the NA enhanced CPP. These data are consistent with the hypothesis that the hedonic effects of T may be due to actions of its metabolites in the NA. (C) 2002 Elsevier Science Inc. All rights reserved.