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

Abstract

The clomipramine (CLI) model of depression was used to examine whether exercise has antidepressant-like effects. Male Sprague-Dawley pups were injected with CLI-HCl (40 mg/kg/day) from age 8 to 21 days. At age 4 weeks, rats were assigned to one of five conditions: (1) sedentary; (2) 24-h access to an activity wheel; (3) sedentary + imipramine-HCl (10 mg/kg/twice daily) during the last 10 days of the experiment; (4) wheel running + imipramine; (5) daily treadmill running. At age 16 weeks, rats underwent sex behavior testing. The rate of copulation was lower in the sedentary CLI-treated group than in the saline controls. Reductions in measures of sexual arousal and levels of monoamines were consistent with the CLI model of depression but were smaller than expected. Wheel runners had more frequent mounts, intromissions, and ejaculations relative to the other groups. Norepinephrine levels in brain frontal cortex were higher in all running groups and the imipramine group relative to the sedentary CLI and saline groups. Radioligand [125I] binding density (BMax) of β-adrenoceptors in frontal cortex was lower for the wheel running, imipramine, and wheel running + imipramine groups. Activity wheel running equaled imipramine treatment for increasing norepinephrine and decreasing BMax, and it exceeded imipramine treatment for increasing male copulatory performance. We conclude that activity wheel running favorably influences several hallmark pharmaco-physiological and behavioral measures of an antidepressant effect but did not alter sexual arousal, a surrogate measure of anhedonia. The weaker than expected effects of CLI treatment indicate that the generalizability of the CLI model requires further elucidation using convergent behavioral, biochemical, and pharmacological measures.