A role for α₁-adrenergic receptors in extinction of conditioned fear and cocaine conditioned place preference.

Abstract

Previous work has demonstrated an important role for adrenergic receptors in memory processes in fear and drug conditioning paradigms. Recent studies have also demonstrated alterations in extinction in these paradigms using drug treatments targeting beta- and alpha2-adrenergic receptors, but little is known about the role of alpha-adrenergic receptors in extinction. The current study examined whether antagonism of alpha-adrenergic receptors would impair the consolidation of extinction in fear and cocaine conditioned place preference paradigms. After contextual fear conditioning, injections of the alpha-adrenergic receptor antagonist prazosin (1.0 or 3.0 mg/kg) following nonreinforced context exposures slowed the loss of conditioned freezing over the course of 5 extinction sessions (Experiment 1). After cocaine place conditioning, prazosin had no effect on the rate of extinction over 8 nonreinforced test sessions. Following postextinction reconditioning, however, prazosin-treated mice showed a robust place preference, but vehicle-treated mice did not, suggesting that prazosin reduced the persistent effects of extinction (Experiment 2). These results confirm the involvement of the alpha-adrenergic receptor in extinction processes in both appetitive and aversive preparations.