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- Title
Inhibition of β-Adrenergic Receptors Induces a Persistent Deficit in Retrieval of a Cocaine-Associated Memory Providing Protection against Reinstatement.
- Authors
Otis, James M; Mueller, Devin
- Abstract
Drug-seeking behavior is maintained by encounters with drug-associated cues. Preventing retrieval of drug-associated memories that these cues provoke would therefore limit relapse susceptibility; however, little is known regarding the mechanisms of retrieval. Here, we show that β-adrenergic receptor activation is necessary for the retrieval of a cocaine-associated memory. Using a conditioned place preference (CPP) procedure, rats were conditioned to associate one chamber, but not another, with cocaine. When administered before a CPP trial, propranolol, but not saline, prevented retrieval of a cocaine-associated CPP. In subsequent drug-free trials, rats previously treated with propranolol continued to show a retrieval deficit, as no CPP was evident. This retrieval deficit was long lasting and robust, as the CPP did not re-emerge during a test for spontaneous recovery 14 days later or reinstate following a priming injection of cocaine. Moreover, the peripheral β-adrenergic receptor antagonist sotalol did not affect retrieval. Thus, retrieval of cocaine-associated memories is mediated by norepinephrine acting at central β-adrenergic receptors. Our findings support the use of propranolol, a commonly prescribed β-blocker, as an adjunct to exposure therapy for the treatment of addiction by preventing retrieval of drug-associated memories during and long after treatment, and by providing protection against relapse.
- Subjects
ADRENERGIC receptors; PROPRANOLOL; PSYCHOLOGY of drug addiction; LABORATORY rats; COCAINE &; psychology; ANIMAL models of drug abuse
- Publication
Neuropsychopharmacology, 2011, Vol 36, Issue 9, p1912
- ISSN
0893-133X
- Publication type
Article
- DOI
10.1038/npp.2011.77