Abstract

Rationale Sexual side effects of chronic treatment with selective serotonin reuptake inhibitors (SSRIs) in humans include anorgasmia and loss of sexual desire and/or arousal which interferes with treatment compliance. There are few options at present to reduce these effects. Because orgasm and desire are mediated in part by activation of sympathetic arousal, we asked whether the sympathomimetic effects of acute caffeine treatment could reverse these effects. Objective The present study examined whether acute treatment with caffeine (CAF; 10 or 20 mg/kg, ip) versus vehicle could ameliorate the disruption of appetitive and consummatory measures of copulatory behavior produced by chronic fluoxetine (10 mg/kg, sc) in adult, sexually active female or male rats. Methods Sexually experienced female or male rats received daily injections of FLU over a 24-day period and were tested for sexual behaviors five times at 4-day intervals during this period in bilevel pacing chambers. Females had been ovariectomized and given hormone replacement with estradiol benzoate and progesterone prior to each test. Males were left gonadally intact. Four days after the final FLU test, rats were randomly assigned to one of the three doses of CAF and received ip injections of CAF or the saline vehicle 60 min before testing. Results Chronic FLU reduced solicitations and lordosis over time in females and reduced the number of ejaculations in males. Both doses of CAF restored solicitations and lordosis in females and ejaculations in males. On their own, both doses of CAF increased females' pacing behavior and the number of mounts and intromissions in the males. Conclusions Stimulation of sympathetic outflow by CAF may constitute a readily accessible on-demand treatment for the sexual side-effects of SSRIs.