Behavioural and biochemical studies of citalopram and WAY 100635 in rat chronic mild stress model

Reversal of chronic mild stress (CMS)-induced decrease of sucrose consumption has been studied in rats after 2, 7, 14, and 35 days treatment with imipramine, citalopram (both 10 mg/kg per day, ip), WAY 100635 (0.2 mg/kg sc, b.i.d.), and citalopram plus WAY 100635. B-max, K-d, and functional status [cyclic AMP (cAMP) generation] of beta(1)-adrenoceptors were assessed in cortical tissue at the same time points. Citalopram reversed CMS-induced reduction of sucrose intake at an earlier time point than imipramine. WAY 100635 was not effective and did not potentiate the effect of citalopram. CMS produced increase of B-max. Imipramine decreased Bmax in controls (days 2, 7, 14, and 35) and normalised Bmax in stressed animals (Day 35). Citalopram, WAY 100635, and the combination increased B-max in stressed animals and controls (Days 14 and 35). Inconsistent changes of K-d values and of cAMP responses to noradrenaline (NA) stimulation were observed. Thus stress- and drug-induced effects on beta1-adrenoceptors do not appear to be a common biochemical marker of antidepressant-like activity in the CMS model. (C) 2002 Published by Elsevier Science Inc.