Hormone replacement with 17β-estradiol plus dihydrotestosterone restores male sexual behavior in rats treated neonatally with clomipramine

Male sexual behavior (MSB) in rodents, in both its consummatory and motivational components, is regulated by hormones such as testosterone, 17β-estradiol and 5-α-dihydrotestosterone. In experiments, neonatal treatment with clomipramine (CMI; a serotonin reuptake inhibitor) reproduces some of the signs of depression in adult age, including reduced sexual behavior manifested in a lower percentage of subjects that mount, intromit and ejaculate, although their testosterone levels were not altered. However, the effect of this treatment on estrogen levels and the consequences of hormone substitution using 17β-estradiol and 5-α-dihydrotestosterone on the expression of male sexual behavior are still unknown. Therefore, the objective of the present study was to analyze the effect of neonatal treatment with CMI on plasma testosterone and 17β-estradiol levels, and the role of testosterone, 17β-estradiol and 5-α-dihydrotestosterone in altering the consummatory and motivational components of sexual behavior in male rats. To this end, it analyzed the copulatory parameters and sexual incentive motivation (SIM) of rats treated with CMI under two conditions: basal and post-hormone replacements. Neonatal treatment with CMI did not affect plasma testosterone or 17β-estradiol concentrations, but did decrease both the consummatory component and sexual motivation according to the results of the SIM test. These aspects were recovered after administering 17β-estradiol +5-α-dihydrotestosterone, but not testosterone. •Neonatal treatment with CMI causes deterioration of sexual behavior and motivation.•Sexual experience did not modify motivation in adult males rats treated with CMI.•High doses of E2 restore sexual motivation in adult male rats with CMI treatment.•The combination of E2 and DHT normalizes sexual behavior patterns in CMI rats.