EN
Cerebral α1-adrenoceptors (α1-AR) are known to be changed by stress conditions and involved inthe mechanism of antidepressant action. The chronic mild stress (CMS) procedure that induces depression-like symptoms in animals is a useful tool to study the mechanisms of action of antidepressant drugs in animals. We aimed to investigate the expression of α1A-, α1B-, and α1D-AR mRNAs in the hippocampus of rats subjected to the standard CMS procedure and then treated with an antidepressant drug, imipramine (IMI). Five groups of male Wistar rats were considered in the study: sham-saline; stress-saline; sham-IMI; stress-IMI and IMI-non-responders (i.e., stressed rats, which did not respond to IMI treatment). The expression of α1-ARs was measured at the level of mRNA (by quantitative real-time PCR) and their total density analyzed by [3H]prazosin autoradiography. We found that both CMS procedure and IMI-treatment did not affect the expression of all α1-AR mRNAs. However, in rats non-responding to IMI treatment in behavioral test, the expression of α1A- , α1B- and α1D-AR mRNAs was signifi cantly increased (respectively, by 81%, P<0.01 78%, P<0.01; 46%, P<0.5) compared to sham-saline and stressIMI groups. Similar direction of change was seen in α1-AR total density. Our results suggest the involvement of all subtypes of α1- adrenoceptor in the phenomenon of resistance of depressive animal to IMI treatment. Supported by statutory funds of the Institute of Pharmacology, PAS.