Failure of neonatal clomipramine treatment to alter forced swim immobility: chronic treadmill or activity-wheel running and imipramine

We examined whether chronic running on a treadmill or activity wheel would attenuate the increased swim immobility that has been reported after neonat al clomipramine (CLI) treatment. Male Sprague-Dawley pups (N = 60) were inj ected with the monoamine reuptake inhibitor clomipramine hydrochloride (40 mg/kg per day i.p.) from 8 to 21 days of age. Another group (N = 12) receiv ed saline vehicle. At age 4 weeks, the CLI pups were randomly assigned to e xperimental conditions: (1) sedentary; (2) 24-h access to an activity wheel ; (3) sedentary that received the antidepressant drug imipramine hydrochlor ide (10 mg/kg twice daily) during the last 10 days of the experiment; (4) a ctivity wheel + imipramine; (5) treadmill running (30 m/min for 1 h at 0 de grees incline, 6 days/week). At age 16 weeks, rats underwent the Porsolt sw im test 48 h after the last imipramine injection and/or the last exercise s ession. The increase in swim immobility among CLI-treated rats was small to ne quarter of SD) and not statistically significant (p > 0.10). The results are not consistent with our previous finding of antidepressant-like effect s of activity-wheel running based on brain noradrenergic adaptations and en hanced male copulatory performance after neonatal CLI treatment. The lack o f change in swim performance after clomipramine questions the generalizabil ity of the CLI model of depression and the validity of the forced swim test as a behavioral measure of depression when it is used after neonatal CLI i njection or chronic activity-wheel running. (C) 2000 Elsevier Science Inc. All rights reserved.