Opiate withdrawal has been associated with up-regulation of α 2 -adrenoceptors (mainly the α 2 A -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 α 2 a -adrenoceptor gene expression as the molecular mechanism underlying the opiate withdrawal-induced up-regulation of α 2 A -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 α 2 a -adrenoceptor mRNA (Northern and dot-blot analyses) in the cerebral cortex. Acute and chronic morphine treatments did not alter significantly the expression of cortical α 2 a -adrenoceptor mRNA. The results indicate that the opiate abstinence syndrome is associated with a transcriptional activation of the α 2 a -adrenoceptor mRNA which can explain the up-regulation of brain α 2 A -adrenoceptors during opiate withdrawal.