title: Dissociation of β1- and β2-adrenergic receptor subtypes in the retrieval of cocaine-associated memory.
abstract: Drug seeking is maintained by encounters with drug-associated cues, and disrupting retrieval of these drug-cue associations would reduce the risk of relapse. Retrieval of cocaine-associated memories is dependent on β-adrenergic receptor (β-AR) activation, and blockade of these receptors induces a persistent retrieval deficit. Whether retrieval of cocaine-associated memory is mediated by a specific β-AR subtype, however, remains unclear. Using a cocaine conditioned place preference (CPP) procedure, we examined whether retrieval of a cocaine CPP memory is mediated collectively by β1- and β2-ARs, or by one of these β-AR subtypes alone. We show that co-blockade of β1- and β2-ARs abolished CPP expression on that and subsequent drug-free CPP tests, resulting in a long-lasting retrieval deficit that prevented subsequent cocaine-induced reinstatement. To dissociate the necessity of either β1- or β2-ARs alone, we administered subtype-specific antagonists prior to retrieval. Administration of a β1-AR antagonist before the initial CPP trial dose-dependently reduced expression of a CPP on that and subsequent drug-free trials as compared to vehicle administration. In contrast, administration of a β2-AR antagonist had no effect on initial CPP expression, although the highest dose reduced subsequent CPP expression. Importantly, either β1- or β2-AR blockade prior to an initial retrieval trial prevented subsequent cocaine-induced reinstatement. Our findings indicate that the β1-AR subtype mediates retrieval of a cocaine CPP, and that acutely blocking either β1- or β2-ARs can prevent subsequent cocaine-induced reinstatement. Thus, β-AR antagonists, particularly β1-ARs antagonists, could serve as adjuncts for addiction therapies to prevent retrieval of drug-associated memories and provide protection against relapse.
authors: Department of Psychology, University of Wisconsin-Milwaukee, Milwaukee, WI 53211, United States.
authors: Michael K
authors: MK
authors: Fitzgerald
authors: Department of Psychology, University of Wisconsin-Milwaukee, Milwaukee, WI 53211, United States.
authors: James M
authors: JM
authors: Otis
authors: Department of Psychology, University of Wisconsin-Milwaukee, Milwaukee, WI 53211, United States. Electronic address: devinm@uwm.edu.
authors: Devin
authors: D
authors: Mueller
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D058672:Adrenergic beta-2 Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D058999:Drug-Seeking Behavior / Q000187:drug effects / Q000502:physiology*; D008297:Male; D011939:Mental Recall / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D020318:Rats, Long-Evans; D018342:Receptors, Adrenergic, beta-1 / Q000187:drug effects / Q000378:metabolism*; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects / Q000378:metabolism*
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D058672:Adrenergic beta-2 Receptor Antagonists; D018765:Dopamine Uptake Inhibitors; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D003042:Cocaine
keywords: Betaxolol; Cocaine-induced reinstatement; Drug abuse; ICI 118,551; Memory retrieval; Noradrenergic beta-receptor; Norepinephrine; Relapse