Antidepressant-like effects of physical activity versus imipramine: Neonatal clomipramine model

The clomipramine (CLI) model of depression was used to examine whether exer cise has antidepressant-like effects. Male Sprague-Dawley pups were injecte d with CLI-HCl (40 mg/kg/day) from age 8 to 21 days. At age 4 weeks, rats w ere assigned to one of five conditions: (1) sedentary; (2) 24-h access to a n activity wheel; (3) sedentary + imipramine-HCl (10 mg/kg/twice daily) dur ing the last 10 days of the experiment; (4) wheel running + imipramine; (5) daily treadmill running. At age 16 weeks, rats underwent sex behavior test ing. The rate of copulation was lower in the sedentary CLI-treated group th an in the saline controls. Reductions in measures of sexual arousal and lev els of monoamines were consistent with the CLI model of depression but were smaller than expected. Wheel runners had more frequent mounts, intromissio ns, and ejaculations relative to the other groups. Norepineplurine levels i n brain frontal cortex were higher in all running groups and the imipramine group relative to the sedentary CLI and saline groups. Radioligand [I-125] binding density (B-Max) of beta -adrenoceptors in frontal cortex was lower for the wheel running, imipramine, and wheel running + imipramine groups. Activity wheel running equaled imipramine treatment for increasing norepine phrine and decreasing B-Max, and it exceeded imipramine treatment for incre asing male copulatory performance. We conclude that activity wheel running favorably influences several hallmark pharmaco-physioiogical and behavioral measures of an antidepressant effect but did not alter sexual arousal, a s urrogate measure of anhedonia. The weaker than expected effects of CLI trea tment indicate that the generalizability of the CLI model requires further elucidation using convergent behavioral, biochemical, and pharmacological m easures.