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The role of kappa opioid receptors in stress-induced reinstatement of alcohol seeking in rats.
Brain Behav. 2014 May; 4(3):356-67.BB

Abstract

INTRODUCTION

Stress is related to heavy alcohol use and relapse in alcoholics. Using the reinstatement model, we have shown that corticotropin-releasing factor (CRF) underlies stress-induced relapse to alcohol seeking in laboratory rodents. Little is known about how other neurotransmitters interact with CRF in these effects. Dynorphin and its receptor (kappa opioid receptor, KOR) are involved in stress responses and in alcohol seeking. KOR and CRF receptors (CRF R) may interact in the production of stress-related behaviors but it is not known whether this interaction is involved in reinstatement of alcohol seeking.

METHODS

Male Long Evans rats were trained to self-administer alcohol (12% w/v). After extinction of responding, we determined the effects of the KOR agonist, U50,488 (2.5, 5 mg/kg) on reinstatement of alcohol seeking, and their sensitivity to the selective KOR antagonist nor-binaltorphimine dihydrochloride (nor-BNI) (10 mg/kg) administered at different times before U50,488. We then examined the effects of nor-BNI on reinstatement induced by the stressor yohimbine (1.25 mg/kg) and on reinstatement induced by exposure to alcohol-associated cues. Finally, we determined whether CRF R1 blockade with antalarmin (10, 20 mg/kg) attenuates alcohol seeking induced by U50,488.

RESULTS

U50,488 reinstated alcohol seeking. Prior treatment with nor-BNI 2, but not 24 h before administration of U50,488 or yohimbine blocked reinstatement induced by these drugs. Cue-induced reinstatement was blocked by nor-BNI administered 2 h prior to testing. Finally, U50,488-induced reinstatement was blocked by antalarmin.

CONCLUSIONS

These data further support a role for KOR in reinstatement of alcohol seeking under nonstress and stressful conditions and that KOR and CRF R interact in these effects.

Authors+Show Affiliations

Neurobiology of Alcohol Laboratory, Centre for Addiction and Mental Health Toronto, Canada.Neurobiology of Alcohol Laboratory, Centre for Addiction and Mental Health Toronto, Canada.Neurobiology of Alcohol Laboratory, Centre for Addiction and Mental Health Toronto, Canada ; Department of Pharmacology, University of Toronto Toronto, Canada ; Department of Psychiatry, University of Toronto Toronto, Canada.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

24944865

Citation

Funk, Douglas, et al. "The Role of Kappa Opioid Receptors in Stress-induced Reinstatement of Alcohol Seeking in Rats." Brain and Behavior, vol. 4, no. 3, 2014, pp. 356-67.
Funk D, Coen K, Lê AD. The role of kappa opioid receptors in stress-induced reinstatement of alcohol seeking in rats. Brain Behav. 2014;4(3):356-67.
Funk, D., Coen, K., & Lê, A. D. (2014). The role of kappa opioid receptors in stress-induced reinstatement of alcohol seeking in rats. Brain and Behavior, 4(3), 356-67. https://doi.org/10.1002/brb3.222
Funk D, Coen K, Lê AD. The Role of Kappa Opioid Receptors in Stress-induced Reinstatement of Alcohol Seeking in Rats. Brain Behav. 2014;4(3):356-67. PubMed PMID: 24944865.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The role of kappa opioid receptors in stress-induced reinstatement of alcohol seeking in rats. AU - Funk,Douglas, AU - Coen,Kathleen, AU - Lê,A D, Y1 - 2014/02/17/ PY - 2013/11/11/received PY - 2014/01/09/revised PY - 2014/01/18/accepted PY - 2014/6/20/entrez PY - 2014/6/20/pubmed PY - 2014/6/20/medline KW - Alcohol self-administration KW - CRF receptors KW - conditioned cue KW - kappa opioid receptors KW - reinstatement KW - stress SP - 356 EP - 67 JF - Brain and behavior JO - Brain Behav VL - 4 IS - 3 N2 - INTRODUCTION: Stress is related to heavy alcohol use and relapse in alcoholics. Using the reinstatement model, we have shown that corticotropin-releasing factor (CRF) underlies stress-induced relapse to alcohol seeking in laboratory rodents. Little is known about how other neurotransmitters interact with CRF in these effects. Dynorphin and its receptor (kappa opioid receptor, KOR) are involved in stress responses and in alcohol seeking. KOR and CRF receptors (CRF R) may interact in the production of stress-related behaviors but it is not known whether this interaction is involved in reinstatement of alcohol seeking. METHODS: Male Long Evans rats were trained to self-administer alcohol (12% w/v). After extinction of responding, we determined the effects of the KOR agonist, U50,488 (2.5, 5 mg/kg) on reinstatement of alcohol seeking, and their sensitivity to the selective KOR antagonist nor-binaltorphimine dihydrochloride (nor-BNI) (10 mg/kg) administered at different times before U50,488. We then examined the effects of nor-BNI on reinstatement induced by the stressor yohimbine (1.25 mg/kg) and on reinstatement induced by exposure to alcohol-associated cues. Finally, we determined whether CRF R1 blockade with antalarmin (10, 20 mg/kg) attenuates alcohol seeking induced by U50,488. RESULTS: U50,488 reinstated alcohol seeking. Prior treatment with nor-BNI 2, but not 24 h before administration of U50,488 or yohimbine blocked reinstatement induced by these drugs. Cue-induced reinstatement was blocked by nor-BNI administered 2 h prior to testing. Finally, U50,488-induced reinstatement was blocked by antalarmin. CONCLUSIONS: These data further support a role for KOR in reinstatement of alcohol seeking under nonstress and stressful conditions and that KOR and CRF R interact in these effects. SN - 2162-3279 UR - https://www.unboundmedicine.com/medline/citation/24944865/The_role_of_kappa_opioid_receptors_in_stress_induced_reinstatement_of_alcohol_seeking_in_rats_ L2 - https://doi.org/10.1002/brb3.222 DB - PRIME DP - Unbound Medicine ER -