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Effects of non-contingent cocaine on 3alpha-androstanediol. I. Disruption of male sexual behavior

Kohtz, Amy S., Walf, Alicia A., Frye, Cheryl A.
Physiology & behavior 2019 v.203 pp. 120-127
cocaine, dose response, estradiol, frontal lobe, hippocampus, hypothalamus, males, metabolism, metabolites, motivation, rats, sexual behavior, testosterone
One of the hallmarks of drug abuse is a reduction in the salience of, and motivation for, natural rewards, such as mating. The effects of psychostimulants on male sexual interest and performance are conflicting; use of psychostimulants can produce increases in risky sexual behaviors but have detrimental effects on sexual ability. We hypothesize that these conflicting effects on sexual behavior are due to interactions between cocaine and androgens, such as testosterone and its neuroactive metabolite, 3α-androstanediol (3α-diol). Male rats were administered saline or cocaine (5, 10, or 20mg/kg, i.p.). Motor behavior was observed in the first 30min following drug-administration, and then sexual responding was assessed for 15min. Levels of androgens (testosterone, 3ɑ-diol, and testosterone's aromatized metabolite, estradiol) were measured in circulation and brain regions (frontal cortex, hippocampus, hypothalamus/striatum (hypo/str), and midbrain). Cocaine had no effect on measures of sexual interest (i.e. anogenital investigation). However, cocaine had substantial effects on consummatory sexual behaviors, such as the latency to mount/intromit and the number of sexual contacts. Frontal cortex and hypo/str 3α-diol levels were strongly correlated with consummatory behaviors in saline administered rats; however, this relationship was disrupted by cocaine at all dosages, concomitant with impaired sexual behaviors. Additionally, there was a shift in metabolism at low dosages of cocaine to push testosterone metabolism in the midbrain towards 3α-diol. On the contrary, moderate and high dosages of cocaine shifted testosterone metabolism towards estradiol. These data demonstrate that the association between cortical and hypo/str 3α-diol levels and sexual behavior of male rats is disrupted by non-contingent cocaine and that there may be dose-dependent effects of acute cocaine on androgen metabolism.