Impact of clomipramine prenatal exposure on sexual behavior and reproductive organs in female rats: role of sexual experience

Depression is a psychiatric disorder that is twice as common in women as in men, with women in the childbearing age being the most at risk of developing depression during pregnancy or the postpartum period. Consequently, antidepressants have been prescribed even when the evidence suggests possible adverse effects on the neurodevelopment of the offspring, considering that antidepressant drugs can be transferred through breast milk. In this way, postnatal (PN) administration of the tricyclic antidepressant clomipramine (CMI) causes persistent behavioral and neurophysiological alterations during adulthood. Contrarily, a rewarding experience as mating improves motivational and copulatory behavior in rodents; therefore, the purpose was to examine the effect of postnatal CMI treatment on female sexual behavior and reproductive tissues, and if sexual experience improves sexual performance. Female rats were divided in two groups, CMI group (30 mg/Kg) and control group (NaCl 0.9%). Each group received a daily subcutaneous injection with CMI or saline solution from the 8 to 21 PN. Behavioral test and histological analysis were performed at 3 months age. The results indicated that postnatal CMI administration disrupts receptive but not proceptive behaviors. Repeated sexual encounters with males reversed the receptivity impairment in CMI-treated females, as it occurs in control rats. Histological data showed that CMI reduces the population of primordial and primary follicles; however, no morphological modifications were detected in the uterine layers. In conclusion, the data show that even when sexual experience improved copulatory behavior in female rats exposed to CMI during the postnatal period, ovarian development was affected, which could compromise fertility.