REVERSAL BY IMIPRAMINE OF BETA-ADRENOCEPTOR UP-REGULATION INDUCED IN A CHRONIC MILD STRESS MODEL OF DEPRESSION

Male Wistar rats were subjected to a chronic mild stress procedure inv olving different stress stimuli applied for 8 weeks. During this time the consumption of 1% sucrose solution was monitored at weekly interva ls. After the first 3 weeks, when stressed animals displayed a reducti on of sucrose consumption, the control and stressed groups were divide d into subgroups receiving daily placebo or imipramine (10 mg/kg/day) treatment. After 5 weeks of treatment, 24 h after the last injection, the rats were killed and beta-adrenoceptor density and affinity in cor tical membrane preparations and the accumulation of cyclic AMP in cort ical slices stimulated with noradrenaline were assessed. While in stre ssed placebo-treated rats the sucrose consumption remained reduced, in the imipramine-treated group the level of consumption gradually retur ned to control values. The stressed placebo-treated rats also displaye d an increase in cortical beta-adrenoceptor density (by 34%) with no c hanges in affinity, and an increase (22%) in the cyclic AMP response t o noradrenaline in cortical slices. Imipramine, which in non-stressed rats did not affect sucrose intake but depressed the beta-adrenoceptor density and the cyclic AMP response, reversed the stress-induced decr ease in sucrose consumption and the increase in the beta-adrenoceptor density; at physiological noradrenaline concentrations it also reduced the enhanced cyclic AMP response. The results suggest that the chroni c mild stress procedure produces behavioral and biochemical changes co nsistent with a realistic model of depression in animals.