Circulating androgens enhance sensitivity to testosterone self-administration in male hamsters

Young adult men are more likely to abuse steroids than individuals with low testosterone, including women, boys and older men. This suggests that circulating testosterone may enhance sensitivity to exogenous androgens. This hypothesis was tested using intracerebroventricular (i.c.v.) testosterone self-administration in orchidectomized males without testosterone (Orchx, n=8) and in orchidectomized males with chronic physiologic testosterone replacement (Orchx+T, n=8). Beginning 1 week after surgery, hamsters self-administered testosterone for 4 h/day in operant chambers at three doses (0.1, 1.0 and 2.0 microg/microl), each for 8 days. Afterwards, testosterone was replaced with vehicle for 8 days to test extinction. At 1.0 and 2.0 microg/microl, Orchx+T and Orchx males self-administered similar amounts of testosterone. However, at 0.1 microg/microl testosterone, only Orchx+T males showed a significant preference for the active nose-poke (Orchx+T active: 35.1+/-8.4 responses/4 h [mean+/-S.E.M.] vs. inactive: 16.5+/-1.7 responses/4 h, p<0.05; Orchx active: 16.7+/-4.9 responses/4 h vs. inactive: 13.5+/-3.1 responses/4 h, p>0.05). There was little change in operant behavior during extinction in Orchx+T males. However, when vehicle replaced testosterone, Orchx males extinguished their preference for the active nose-poke hole by day 6. These results support our hypothesis that circulating androgens enhance sensitivity to testosterone self-administration.