title: Inhibition of β-adrenergic receptors induces a persistent deficit in retrieval of a cocaine-associated memory providing protection against reinstatement.
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.
authors.affiliation: Department of Psychology, University of Wisconsin-Milwaukee, Milwaukee, WI, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Otis
authors.forename: Devin
authors.initials: D
authors.lastname: Mueller
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D003042:Cocaine / Q000494:pharmacology; D019970:Cocaine-Related Disorders / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D008297:Male; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D008569:Memory Disorders / Q000139:chemically induced* / Q000503:physiopathology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000502:physiology; D011433:Propranolol / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D020318:Rats, Long-Evans; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology; D055502:Secondary Prevention
chemical_list: D000319:Adrenergic beta-Antagonists; D018765:Dopamine Uptake Inhibitors; D011943:Receptors, Adrenergic, beta; D011433:Propranolol; D003042:Cocaine; D009638:Norepinephrine