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Behavioral stress may increase the rewarding valence of cocaine-associated cues through a dynorphin/kappa-opioid receptor-mediated mechanism without affecting associative learning or memory retrieval mechanisms.
Neuropsychopharmacology. 2010 Aug; 35(9):1932-42.N

Abstract

Stress exposure increases the risk of addictive drug use in human and animal models of drug addiction by mechanisms that are not completely understood. Mice subjected to repeated forced swim stress (FSS) before cocaine develop significantly greater conditioned place preference (CPP) for the drug-paired chamber than unstressed mice. Analysis of the dose dependency showed that FSS increased both the maximal CPP response and sensitivity to cocaine. To determine whether FSS potentiated CPP by enhancing associative learning mechanisms, mice were conditioned with cocaine in the absence of stress, then challenged after association was complete with the kappa-opioid receptor (KOR) agonist U50,488 or repeated FSS, before preference testing. Mice challenged with U50,488 60 min before CPP preference testing expressed significantly greater cocaine-CPP than saline-challenged mice. Potentiation by U50,488 was dose and time dependent and blocked by the KOR antagonist norbinaltorphimine (norBNI). Similarly, mice subjected to repeated FSS before the final preference test expressed significantly greater cocaine-CPP than unstressed controls, and FSS-induced potentiation was blocked by norBNI. Novel object recognition (NOR) performance was not affected by U50,488 given 60 min before assay, but was impaired when given 15 min before NOR assay, suggesting that KOR activation did not potentiate CPP by facilitating memory retrieval or expression. The results from this study show that the potentiation of cocaine-CPP by KOR activation does not result from an enhancement of associative learning mechanisms and that stress may instead enhance the rewarding valence of cocaine-associated cues by a dynorphin-dependent mechanism.

Authors+Show Affiliations

Department of Pharmacology, University of Washington School of Medicine, Seattle, WA 98195-7280, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20445500

Citation

Schindler, Abigail G., et al. "Behavioral Stress May Increase the Rewarding Valence of Cocaine-associated Cues Through a Dynorphin/kappa-opioid Receptor-mediated Mechanism Without Affecting Associative Learning or Memory Retrieval Mechanisms." Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, vol. 35, no. 9, 2010, pp. 1932-42.
Schindler AG, Li S, Chavkin C. Behavioral stress may increase the rewarding valence of cocaine-associated cues through a dynorphin/kappa-opioid receptor-mediated mechanism without affecting associative learning or memory retrieval mechanisms. Neuropsychopharmacology. 2010;35(9):1932-42.
Schindler, A. G., Li, S., & Chavkin, C. (2010). Behavioral stress may increase the rewarding valence of cocaine-associated cues through a dynorphin/kappa-opioid receptor-mediated mechanism without affecting associative learning or memory retrieval mechanisms. Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, 35(9), 1932-42. https://doi.org/10.1038/npp.2010.67
Schindler AG, Li S, Chavkin C. Behavioral Stress May Increase the Rewarding Valence of Cocaine-associated Cues Through a Dynorphin/kappa-opioid Receptor-mediated Mechanism Without Affecting Associative Learning or Memory Retrieval Mechanisms. Neuropsychopharmacology. 2010;35(9):1932-42. PubMed PMID: 20445500.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Behavioral stress may increase the rewarding valence of cocaine-associated cues through a dynorphin/kappa-opioid receptor-mediated mechanism without affecting associative learning or memory retrieval mechanisms. AU - Schindler,Abigail G, AU - Li,Shuang, AU - Chavkin,Charles, Y1 - 2010/05/05/ PY - 2010/5/7/entrez PY - 2010/5/7/pubmed PY - 2010/10/29/medline SP - 1932 EP - 42 JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology JO - Neuropsychopharmacology VL - 35 IS - 9 N2 - Stress exposure increases the risk of addictive drug use in human and animal models of drug addiction by mechanisms that are not completely understood. Mice subjected to repeated forced swim stress (FSS) before cocaine develop significantly greater conditioned place preference (CPP) for the drug-paired chamber than unstressed mice. Analysis of the dose dependency showed that FSS increased both the maximal CPP response and sensitivity to cocaine. To determine whether FSS potentiated CPP by enhancing associative learning mechanisms, mice were conditioned with cocaine in the absence of stress, then challenged after association was complete with the kappa-opioid receptor (KOR) agonist U50,488 or repeated FSS, before preference testing. Mice challenged with U50,488 60 min before CPP preference testing expressed significantly greater cocaine-CPP than saline-challenged mice. Potentiation by U50,488 was dose and time dependent and blocked by the KOR antagonist norbinaltorphimine (norBNI). Similarly, mice subjected to repeated FSS before the final preference test expressed significantly greater cocaine-CPP than unstressed controls, and FSS-induced potentiation was blocked by norBNI. Novel object recognition (NOR) performance was not affected by U50,488 given 60 min before assay, but was impaired when given 15 min before NOR assay, suggesting that KOR activation did not potentiate CPP by facilitating memory retrieval or expression. The results from this study show that the potentiation of cocaine-CPP by KOR activation does not result from an enhancement of associative learning mechanisms and that stress may instead enhance the rewarding valence of cocaine-associated cues by a dynorphin-dependent mechanism. SN - 1740-634X UR - https://www.unboundmedicine.com/medline/citation/20445500/Behavioral_stress_may_increase_the_rewarding_valence_of_cocaine_associated_cues_through_a_dynorphin/kappa_opioid_receptor_mediated_mechanism_without_affecting_associative_learning_or_memory_retrieval_mechanisms_ L2 - https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20445500/ DB - PRIME DP - Unbound Medicine ER -