Naloxone-precipitated withdrawal in morphine-dependent rats increases the expression of alpha(2a)-adrenoceptor mRNA in brain

Opiate withdrawal has been associated with up-regulation of alpha(2)-adrenoceptors (mainly the alpha(2A)-subtype) in brain. The modulation of these inhibitory receptors regulating norepinephrine release appears to be a relevant mechanism by which the opiate abstinence syndrome might be counteracted. The aim of this study was to investigate possible changes in alpha(2A)-adrenoceptor gene expression as the molecular mechanism underlying the opiate withdrawal-induced up-regulation of alpha(2A)-adrenoceptors. In morphine-dependent rats (10-100 mg/kg for 5 days), naloxone (2 mg/kg)-precipitated withdrawal induced a rapid (2 h) and marked up-regulation (111%, P < 0.001) in the expression of alpha(2a)-adrenoceptor mRNA (Northern and dot-blot analyses) in the cerebral cortex. Acute and chronic morphine treatments did not alter significantly the expression of cortical alpha(2a)-adrenoceptor mRNA. The results indicate that the opiate abstinence syndrome is associated with a transcriptional activation of the alpha(2a)-adrenoceptor mRNA which can explain the up-regulation of brain alpha(2a)-adrenoceptors during opiate withdrawal.