M. Papp et al., REVERSAL BY IMIPRAMINE OF BETA-ADRENOCEPTOR UP-REGULATION INDUCED IN A CHRONIC MILD STRESS MODEL OF DEPRESSION, European journal of pharmacology, 261(1-2), 1994, pp. 141-147
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.