Abstract
Rationale
Studies suggest that the κ-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 κ-opioidergic system. However, the exact role of κ-opioid receptors on regulating ethanol intake and contribution to the development of ethanol addiction remains to be elucidated.
Objectives
The aim of the present study was to clarify the role of accumbal κ-opioid receptors in controlling ethanol intake in alcohol-preferring Alko Alcohol (AA) rats.
Methods
Microinfusions of the long-acting and selective κ-opioid receptor antagonist JDTic (1–15 μg/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 μg/site) was administered intra-accumbally.
Results
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.
Conclusions
The results provide further evidence that κ-opioid receptors play a role in controlling ethanol intake and that accumbal κ-opioid receptors participate in the modulation of the reinforcing effects of ethanol. Furthermore, the results suggest that κ-opioid receptor antagonists may be a valuable adjunct in the pharmacotherapy of ethanol use disorders.
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Acknowledgements
We thank Ms. Leena Tanner-Väisänen for her excellent technical assistance. The authors would also like to thank RTI International (Research Triangle Park, NC, USA) for generously providing the JDTic to be used in these experiments. This study was supported by the Finnish Foundation for Alcohol Studies. The authors declare that they do not have any conflicts of interest related to the data presented in this manuscript. The experiments comply with the current laws of the country in which they were performed.
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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.
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This study was supported by the Finnish Foundation for Alcohol Studies. JDTic was provided as a gift from RTI International (Research Triangle Park, NC, USA). The authors declare that they have no conflicts of interest.
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Uhari-Väänänen, J., Raasmaja, A., Bäckström, P. et al. The κ-opioid receptor antagonist JDTic decreases ethanol intake in alcohol-preferring AA rats. Psychopharmacology 235, 1581–1591 (2018). https://doi.org/10.1007/s00213-018-4868-x
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DOI: https://doi.org/10.1007/s00213-018-4868-x