A role for alpha-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.

Figure 1

Effects of post-session prazosin injections on extinction of context-evoked fear. Sessions 1–3 of extinction consisted of a 3-min nonreinforced context exposure; sessions 4–6 consisted of a 12-min exposure. Each of the first five sessions was followed by an IP injection of 1.0 mg/kg prazosin (n=26), 3.0 mg/kg prazosin (n=15), or vehicle (n=15). Error bars represent standard error of the mean.

Figure 2

Effects of post-session prazosin injections on extinction of cocaine-induced conditioned place preference. (A) Percent time spent on the cocaine-paired floor is shown for the eight sessions of extinction and for the two test sessions following post-extinction reconditioning (RC) with 5 mg/kg (RC5) or 20 mg/kg (RC20) of cocaine. Each of the extinction sessions was followed by IP injection of 1.0 mg/kg prazosin (n=15), 3.0 mg/kg prazosin (n=16), or vehicle (n=16). Mean time spent on the GRID floor during (B) the first and last extinction session and (C) the two sessions following reconditioning is shown for mice that received cocaine pairings with the GRID floor (G+) and mice that received pairings with the HOLE floor (G−). Error bars represent standard error of the mean.