Research ReportsThe role of opioidergic system in modulating cost/benefit decision-making in alcohol-preferring AA rats and Wistar ratsOinio, Villea,,b; Sundström, Mikkoa; Bäckström, Piab; Uhari-Väänänen, Johannaa,,b; Kiianmaa, Kalervob; Raasmaja, Atsoa; Piepponen, Petteria Author Information aDepartment of Pharmacology and Pharmacotherapy, Faculty of Pharmacy, University of Helsinki bDepartment of Health, National Institute for Health and Welfare, Helsinki, Finland Received 7 April 2020 Accepted as revised 30 September 2020 Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website, www.behaviouralpharm.com. Correspondence to Ville Oinio, MSc, Department of Pharmacology and Pharmacotherapy, Faculty of Pharmacy, P.O. Box 56, University of Helsinki, Helsinki, 00014, Finland, E-mail: [email protected] Behavioural Pharmacology: April 2021 - Volume 32 - Issue 2&3 - p 220-228 doi: 10.1097/FBP.0000000000000606 Buy SDC Metrics Abstract Research has highlighted the association of a positive family history of alcoholism with a positive treatment response to opioid antagonists in those with a gambling disorder. However, the role of the opioidergic system in gambling behavior is not well understood, and preclinical studies are needed to clarify this. In this study, Alko Alcohol (AA) and Wistar rats went through operant lever pressing training where the task was to choose the more profitable of two options. Different sized sucrose rewards guided the lever choices, and the probability of gaining rewards changed slowly to a level where choosing the smaller reward was the most profitable option. After training, rats were administered subcutaneously with opioid agonist morphine or opioid antagonist naltrexone to study the impact of opioidergic mechanisms on cost/benefit decisions. No difference was found in the decision-making between AA rats or Wistar rats after the morphine administration, but control data revealed a minor decision enhancing effect in AA rats. Naltrexone had no impact on the decisions in AA rats but promoted unprofitable decisions in Wistar rats. Supporting behavioral data showed that in both rat strains morphine increased, and naltrexone decreased, sucrose consumption. Naltrexone also increased the time to accomplish the operant task. The results suggest that opioid agonists could improve decision-making in cost-benefit settings in rats that are naturally prone to high alcohol drinking. The naltrexone results are ambiguous but may partly explain why opioid antagonists lack a positive pharmacotherapeutic effect in some subgroups of gamblers. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.