Prazosin differentially affects extinction of cocaine conditioned place preference on the basis of dose and initial preference.

Recent work has shown that α1-adrenergic receptor blockade impairs extinction in fear conditioning paradigms in rodents. However, studies of the role of α1-adrenergic receptors in extinction using other conditioning paradigms, such as those examining the conditioned effects of drug of abuse, have yielded inconsistent results. In this article, we reanalyze and extend previously reported findings of the effect of prazosin, an α1-adrenergic receptor antagonist, on the extinction of a cocaine-induced conditioned place preference in rats, using a median split of performance during the initial test for preference. This new reanalysis, which includes further extinction testing, indicated a paradoxical dose effect. A single post-test administration of a lower dose of prazosin, 0.3 mg/kg intraperitoneally, impaired extinction in rats that showed a below-median preference during initial testing, but had no effect on extinction in rats that showed an above-median preference during initial testing. In contrast, a single post-test administration of a higher dose of prazosin, 1.0 mg/kg intraperitoneally, enhanced extinction in rats that showed an above-median preference during initial testing, but had no effect on extinction in rats that showed a below-median preference during initial testing. Consistent with other studies of fear and drug conditioning, these results suggest the involvement of the α1-adrenergic receptor in the formation of extinction memories, but also indicate a potentially important differential effect on extinction on the basis of the dose of prazosin and the strength of the initial learning.