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

Behav Brain Funct. 2026 Jul 3. doi: 10.1186/s12993-026-00352-y. Online ahead of print.

ABSTRACT

Depression is a common psychiatric disorder during pregnancy and the postnatal period. Consequently, antidepressant treatment is primordial for the safety of the mother and the neonate. Clomipramine (CMI) is a tricyclic antidepressant that has been prescribed even when the evidence suggests potential adverse effects on the neurodevelopment of the offspring, considering that antidepressant drugs can be transferred through breast milk. Nevertheless, in some cases, when the benefits outweigh the risks, it is used to treat severe depression in pregnant women. In rodents, postnatal administration of CMI causes persistent behavioral and neurophysiological alterations in adulthood. By contrast, a rewarding experience, such as mating, improves motivational and copulatory behavior in rodents through neuroplasticity in brain structures involved in reproduction. In a previous work, we reported that postnatal exposure to CMI disrupts the motivational and copulatory components of female sexual behavior during a single copulatory test. Therefore, the purpose of this study was to examine the effects of postnatal CMI treatment on female sexual behavior and reproductive tissues, and to determine whether sexual experience serves as a modulatory factor that ameliorates its potential impact on sexual performance. Female pups were divided in two groups, CMI group (30 mg/Kg) and the control group (NaCl 0.9%). Each group received a daily subcutaneous injection with CMI or saline solution from the 8th to 21st postnatal days. Behavioral test and histological analysis were performed at 3 months of age. The results indicated that postnatal CMI administration disrupts receptive but not proceptive behaviors. Repeated sexual encounters with males partially 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 partially improved copulatory behavior in female rats exposed to CMI during the postnatal period, ovarian development was affected, which could compromise fertility.

PMID:42399987 | DOI:10.1186/s12993-026-00352-y