The κ-opioid receptor antagonist JDTic decreases ethanol intake in alcohol-preferring AA rats

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Uhari-Väänänen , J , Raasmaja , A , Bäckström , P , Oinio , V , Carroll , F I , Airavaara , M , Kiianmaa , K & Piepponen , P 2018 , ' The κ-opioid receptor antagonist JDTic decreases ethanol intake in alcohol-preferring AA rats ' , Psychopharmacology , vol. 235 , no. 5 , pp. 1581-1591 . https://doi.org/10.1007/s00213-018-4868-x

Title: The κ-opioid receptor antagonist JDTic decreases ethanol intake in alcohol-preferring AA rats
Author: Uhari-Väänänen, Johanna; Raasmaja, Atso; Bäckström, Pia; Oinio, Ville; Carroll, F. Ivy; Airavaara, Mikko; Kiianmaa, Kalervo; Piepponen, Petteri
Contributor: University of Helsinki, Faculty of Pharmacy
University of Helsinki, Division of Pharmacology and Pharmacotherapy
University of Helsinki, Faculty of Pharmacy
University of Helsinki, Institute of Biotechnology
University of Helsinki, Faculty of Pharmacy
Date: 2018-05
Language: eng
Number of pages: 11
Belongs to series: Psychopharmacology
ISSN: 0033-3158
URI: http://hdl.handle.net/10138/308977
Abstract: Studies suggest that the kappa-opioidergic system becomes overactivated as ethanol use disorders develop. Nalmefene, a currently approved treatment for ethanol use disorders, may also elicit some of its main effects via the kappa-opioidergic system. However, the exact role of kappa-opioid receptors on regulating ethanol intake and contribution to the development of ethanol addiction remains to be elucidated. The aim of the present study was to clarify the role of accumbal kappa-opioid receptors in controlling ethanol intake in alcohol-preferring Alko Alcohol (AA) rats. Microinfusions of the long-acting and selective kappa-opioid receptor antagonist JDTic (1-15 mu g/site) were administered bilaterally into the nucleus accumbens shell of AA rats voluntarily consuming 10% ethanol solution in the intermittent, time-restricted two-bottle choice access paradigm. JDTic (10 mg/kg) was also administered subcutaneously. Both the acute and long-term effects of the treatment on ethanol intake were examined. As a reference, nor-BNI (3 mu g/site) was administered intra-accumbally. Systemically administered JDTic decreased ethanol intake significantly 2 days and showed a similar trend 4 days after administration. Furthermore, intra-accumbally administered JDTic showed a weak decreasing effect on ethanol intake long-term but had no acute effects. Intra-accumbal administration of nor-BNI tended to decrease ethanol intake. The results provide further evidence that kappa-opioid receptors play a role in controlling ethanol intake and that accumbal kappa-opioid receptors participate in the modulation of the reinforcing effects of ethanol. Furthermore, the results suggest that kappa-opioid receptor antagonists may be a valuable adjunct in the pharmacotherapy of ethanol use disorders.
Subject: kappa-Opioid receptor
Intermittent ethanol intake
JDTic
Nor-BNI
Nucleus accumbens shell
Alko Alcohol rat
NUCLEUS-ACCUMBENS SHELL
AVOIDING ANA RATS
LONG-EVANS RATS
MICRODIALYSIS PROFILE
VENTRAL PALLIDUM
WISTAR RATS
DOPAMINE TRANSPORTER
NOR-BINALTORPHIMINE
20-PERCENT ETHANOL
AGONIST U50,488H
3112 Neurosciences
317 Pharmacy
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