Dose-dependent decrements in adult male rat sexual behavior after neonatal clorimipramine treatment

Abstract

Previous studies found that months after clorimipramine (CLI) treatment of male neonatal rats, the mature animals developed behavioral deficits and REM sleep abnormalities that modeled human endogenous depression. In the initial studies neonatal rats received CLI 30 mg/kg/IP daily from age 8 through 21 days. Diminished sexual activity of the adult rats treated neonatally in this manner was a behavioral deficit that supported the depression model. However, in subsequent studies in our laboratory, the same neonatal treatment occasionally failed to produce adult sexual deficiencies found in the initial studies. The inconsistency raised the possibility that neonatal CLI treatment was not a reliable method to produce an animal model of depression. An alternative hypothesis was that the CLI dose was too low. The present study tested this hypothesis. Placebo or one of four CLI doses was administered daily to male neonatal rats ( n = 12/treatment group) from age 8 days through 21 days: 30 (the original dose), 40, 50, and 60 mg/kg/IP. Six components of adult sexual behavior were measured at age 5 months. Deficiency of each sexual behavior was found to be dose-dependent ( r = 0.5, p < 0.001). The 30 mg/kg/day dose caused deficiencies in some, but not all, sexual behavior measures. Higher doses caused deficiencies in all measures of sexual behavior. The results support the hypothesis that neonatal CLI treatment at doses higher than the original 30 mg/kg/day caused reliable impairments in adult male rat sexual behavior, and thereby support the reliability of neonatal CLI treatment to produce an animal model of endogenous depression.