Naltrexone effects on male sexual behavior, corticosterone, and testosterone in stressed male rats

Chronic physical or psychological stress disrupts male reproductive function. Studies in our laboratory have shown that stress by immersion in cold water (ICW) and by electrical foot shocks (EFS) has inhibitory effects on male sexual behavior; these effects do not seem to be mediated by an increase in corticosterone, nor by a decrease in testosterone. On the other hand, it is known that endogenous opioids are released in the brain in response to these same stressors; consequently, they could be participating in the impairment of sexual behavior, as well as in the changes in corticosterone and testosterone caused by stress. The aim of this study was to analyze the effects of the opioid antagonist naltrexone (NTX) on male sexual behavior, corticosterone, and testosterone in both stressed sexually experienced and naive male rats. Sexually experienced adult male rats were assigned to one of the following groups (n=10 each): 1) control group, males without sexual evaluation; 2) control group, rats injected ip with saline, non-stressed; 3) control group, rats injected with NTX (3 mg/kg) non-stressed; 4) rats injected ip with saline, and stressed by EFS; 5) rats injected ip with NTX (1.5 mg/kg) and stressed by EFS; 6) rats injected ip with saline and stressed by ICW; 7) rats injected ip with NTX (1.5 mg/kg) and stressed by ICW; 8) rats injected ip with NTX (3 mg/kg) and stressed by ICW. Naive males were assigned to the same control groups but only stressed by ICW and the NTX dose used was 3 mg/kg. Injections were given 30 min before stress sessions. Stress was applied on 20 consecutive days. Male sexual behavior was assessed 15 min after EFS or 30 min after ICW, on days 1, 4, 8, 12, 15, and 20. Trunk blood was collected at the end of the experiments on day 20 of stress. Corticosterone and testosterone were evaluated by HPLC. Mount, intromission and ejaculation latencies were longer in control saline naive males compared to control saline sexually experienced males on the first day. NTX administration to control naive males caused a decrease in mount, intromission, and ejaculation latencies, as well as an increase in ejaculatory frequency/30 min, compared to control-saline only on day 1. Stressed naive males showed higher mount, intromission and ejaculation latencies, compared to control and stressed sexually experienced males, as well as comparable increase in corticosterone and decrease in testosterone plasma levels. NTX administration before exposure to stress prevented the modifications caused by stress in sexual parameters. Sexual behavior in control sexually-active males injected with saline or NTX was not modified. Saline stressed males showed the previously reported alterations in sexual behavior, as well as an increase in corticosterone and a decrease in testosterone plasma levels. Stressed males injected with NTX before exposure to stress showed no alterations in male sexual behavior. NTX in control non-stressed males did not modify corticosterone plasma levels, but did cause a significant increase in plasma testosterone. The increase in corticosterone and the decrease in testosterone due to stress, were attenuated with the opioid antagonist, both in naive and sexually experienced males. Prevention of ICW stress effects was more effective with higher doses of NTX (3 mg/kg). These data suggest that endogenous opioids could be participating in the effects caused by stress on male sexual behavior, corticosterone, and testosterone.