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 involving different stress stimuli applied for 8 weeks. During this time the consumption of 1% sucrose solution was monitored at weekly intervals. After the first 3 weeks, when stressed animals displayed a reduction of sucrose consumption, the control and stressed groups were divided 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 cortical membrane preparations and the accumulation of cyclic AMP in cortical slices stimulated with noradrenaline were assessed. While in stressed placebo-treated rats the sucrose consumption remained reduced, in the imipramine-treated group the level of consumption gradually returned to control values. The stressed placebo-treated rats also displayed an increase in cortical beta-adrenoceptor density (by 34%) with no changes in affinity, and an increase (22%) in the cyclic AMP response to 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 decrease 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 chronic mild stress procedure produces behavioral and biochemical changes consistent with a realistic model of depression in animals.
Papp
M
M
Institute of Pharmacology, Polish Academy of Sciences, Krakow.
Nalepa
I
I
Vetulani
J
J
D000262:Adenylyl Cyclases / Q000378:metabolism; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D002908:Chronic Disease; D003863:Depression / Q000378:metabolism*; D007099:Imipramine / Q000494:pharmacology*; D008297:Male; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D013315:Stress, Psychological / Q000378:metabolism*; D013395:Sucrose / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects*
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D013395:Sucrose; D000262:Adenylyl Cyclases; D007099:Imipramine; C033394:CGP 12177