Gonadectomy enhances cocaine‐induced locomotor activity in male rats

Abstract

Sex differences in cocaine addiction have been demonstrated in clinical as well as animal studies. However, studies on the role of testosterone in mediating these sex differences are inconclusive. This study investigated the effect of gonadectomy on cocaine‐induced hyperactivity. Adult male rats (300‐320g) were gonadectomized (GDX) or left gonadally intact (INT). Six days later, animals were placed in automated activity cages and their basal locomotor activity (LMA) was recorded. The next day, rats received a saline or cocaine (10, 15 or 30 mg/kg) injection and LMA was recorded.Cocaine increased LMA in both groups. However, this increase was higher in GDX than in INT rats, particularly at doses of 15 and 30 mg/kg. Also, while INT rats show a progressive increase in LMA to the same dose of cocaine (sensitization) at all doses tested, only a dose of 10 mg/kg was effective in inducing behavioral sensitization to cocaine in GDX males. These results show that in the male rat, gonadal hormones participate in mediating neuroadaptations to repeated cocaine administration.Support contributed by: NIH grants: U54NS39405 (SNRP); SO6‐GM08224 (MBRS/SCORE); and R25GM61838 (MBRS/RISE)]