title: Post-retrieval beta-adrenergic receptor blockade: effects on extinction and reconsolidation of cocaine-cue memories.
abstract: 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.
authors.affiliation: Department of Neurobiology and Behavior, Center for the Neurobiology of Learning and Memory, University of California, Irvine, California 92697, USA.
authors.forename: Ashley N
authors.initials: AN
authors.lastname: Fricks-Gleason
authors.forename: John F
authors.initials: JF
authors.lastname: Marshall
mesh_terms: 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
chemical_list: D000319:Adrenergic beta-Antagonists; D018765:Dopamine Uptake Inhibitors; D003042:Cocaine
references.citation: Behav Brain Res. 2006 Sep 15;172(1):173-8
references.pmid: 16769132
references.citation: Learn Mem. 2000 Mar-Apr;7(2):73-84
references.pmid: 10753974
references.citation: Proc Natl Acad Sci U S A. 2006 Feb 28;103(9):3428-33
references.pmid: 16492789
references.citation: J Neurosci. 2006 May 31;26(22):5881-7
references.pmid: 16738229
references.citation: Behav Brain Res. 2000 Oct;115(1):39-47
references.pmid: 10996406
references.citation: Neuropsychopharmacology. 2006 Jan;31(1):160-70
references.pmid: 15886718
references.citation: Neuroreport. 2006 Sep 18;17(13):1443-7
references.pmid: 16932155
references.citation: Neuroreport. 2007 May 28;18(8):777-80
references.pmid: 17471065
references.citation: Q J Exp Psychol B. 2004 Apr;57(2):97-132
references.pmid: 15204112
references.citation: Neuron. 2002 Nov 14;36(4):567-84
references.pmid: 12441048
references.citation: NIDA Res Monogr. 1988;81:74-80
references.pmid: 3136393
references.citation: J Neurosci. 2004 Oct 20;24(42):9269-75
references.pmid: 15496662
references.citation: Nat Neurosci. 2001 Aug;4(8):813-8
references.pmid: 11477427
references.citation: Learn Mem. 2008 Jan 29;15(2):88-92
references.pmid: 18235109
references.citation: Neuron. 2005 Sep 15;47(6):873-84
references.pmid: 16157281
references.citation: Prog Neuropsychopharmacol Biol Psychiatry. 1983;7(4-6):591-7
references.pmid: 6686696
references.citation: Behav Brain Res. 2007 Aug 22;182(1):129-34
references.pmid: 17604134
references.citation: Behav Pharmacol. 2007 Nov;18(7):699-703
references.pmid: 17912055
references.citation: Science. 2004 May 7;304(5672):839-43
references.pmid: 15073322
references.citation: Neuroscience. 2004;129(2):267-72
references.pmid: 15501585
references.citation: J Neurosci. 2006 Mar 15;26(11):3010-20
references.pmid: 16540579
references.citation: Behav Brain Res. 2006 Jun 30;170(2):333-6
references.pmid: 16600394
references.citation: Neuron. 2005 Sep 15;47(6):795-801
references.pmid: 16157275