Post-retrieval beta-adrenergic receptor blockade: effects on extinction and reconsolidation of cocaine-cue memories.
Contexts and discrete cues associated with drug-taking are often responsible for relapse among addicts. Animal models have shown that interference with the reconsolidation of drug-cue memories can reduce seeking of drugs or drug-paired stimuli. One such model is conditioned place preference (CPP) in which an animal is trained to associate a particular environment with the rewarding effects of a drug. Previous work from this laboratory has shown that intra-nucleus accumbens core infusions of a MEK inhibitor can interfere with reconsolidation of these drug-cue memories. A question that remains is whether post-retrieval drug effects on subsequent memories represent an interference with reconsolidation processes or rather a facilitation of extinction. In this experiment, we explore the effect of post-retrieval injections of propranolol, a beta-adrenergic receptor antagonist, on reconsolidation and extinction of cocaine CPP. After acquisition of cocaine CPP, animals were given post-retrieval propranolol injections once or each day during a protocol of unreinforced preference tests, until the animals showed no preference for the previously cocaine-paired environment. Following a cocaine priming injection, the animals that received daily post-test propranolol injections did not reinstate their preference for the drug-paired side. In contrast, a single post-retrieval propranolol injection followed by multiple days of unreinforced preference tests failed to blunt subsequent cocaine reinstatement of the memory. These data suggest that daily post-retrieval systemic injections of propranolol decrease the conditioned preference by interfering with reconsolidation of the memory for the association between the drug-paired side and the reinforcing effects of the drug, rather than facilitating new extinction learning.
Fricks-Gleason
Ashley N
AN
Department of Neurobiology and Behavior, Center for the Neurobiology of Learning and Memory, University of California, Irvine, California 92697, USA.
Marshall
John F
JF
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D016739:Behavior, Addictive / Q000188:drug therapy / Q000503:physiopathology*; D001921:Brain / Q000187:drug effects / Q000502:physiology; D003042:Cocaine / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000188:drug therapy / Q000503:physiopathology; D003216:Conditioning, Operant / Q000187:drug effects; D003463:Cues; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D005108:Extinction, Psychological / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008568:Memory / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000319:Adrenergic beta-Antagonists; D018765:Dopamine Uptake Inhibitors; D003042:Cocaine
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