Accumbal μ-Opioid Receptors Modulate Ethanol Intake in Alcohol-Preferring Alko Alcohol Rats

• Published in: Alcoholism, clinical and experimental research Vol. 40; no. 10; pp. 2114 - 2123
• Main Authors: Uhari-Väänänen, Johanna, Raasmaja, Atso, Bäckström, Pia, Oinio, Ville, Airavaara, Mikko, Piepponen, Petteri, Kiianmaa, Kalervo
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.10.2016; Wiley Subscription Services, Inc
• Subjects: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer - pharmacology; Alcohol Drinking - physiopathology; Alko Alcohol Rat; Animals; Dose-Response Relationship, Drug; Enkephalin, Ala-MePhe-Gly- - administration & dosage; Enkephalin, Ala-MePhe-Gly- - pharmacology; Ethanol - administration & dosage; Ethanol Intake; Male; Microinjections; Morphine - administration & dosage; Morphine - pharmacology; Nucleus Accumbens - physiology; Nucleus Accumbens Shell; Rats; Receptors, Opioid, kappa - agonists; Receptors, Opioid, kappa - physiology; Receptors, Opioid, mu - agonists; Receptors, Opioid, mu - antagonists & inhibitors; Receptors, Opioid, mu - physiology; Reward; Somatostatin - administration & dosage; Somatostatin - analogs & derivatives; Somatostatin - pharmacology; Species Specificity; κ-Opioid Receptor; μ-Opioid Receptor; Ethanol Intake; Nucleus Accumbens Shell; μ-Opioid Receptor; Alko Alcohol Rat; κ-Opioid Receptor
• ISSN: 0145-6008; 1530-0277
• DOI: 10.1111/acer.13176

Background The nucleus accumbens shell is a key brain area mediating the reinforcing effects of ethanol (EtOH). Previously, it has been shown that the density of μ‐opioid receptors in the nucleus accumbens shell is higher in alcohol‐preferring Alko Alcohol (AA) rats than in alcohol‐avoiding Alko Non‐Alcohol rats. In addition, EtOH releases opioid peptides in the nucleus accumbens and opioid receptor antagonists are able to modify EtOH intake, all suggesting an opioidergic mechanism in the control of EtOH consumption. As the exact mechanisms of opioidergic involvement remains to be elucidated, the aim of this study was to clarify the role of accumbal μ‐ and κ‐opioid receptors in controlling EtOH intake in alcohol‐preferring AA rats. Methods Microinfusions of the μ‐opioid receptor antagonist CTOP (0.3 and 1 μg/site), μ‐opioid receptor agonist DAMGO (0.03 and 0.1 μg/site), nonselective opioid receptor agonist morphine (30 μg/site), and κ‐opioid receptor agonist U50488H (0.3 and 1 μg/site) were administered via bilateral guide cannulas into the nucleus accumbens shell of AA rats that voluntarily consumed 10% EtOH solution in an intermittent, time‐restricted (90‐minute) 2‐bottle choice access paradigm. Results CTOP (1 μg/site) significantly increased EtOH intake. Conversely, DAMGO resulted in a decreasing trend in EtOH intake. Neither morphine nor U50488H had any effect on EtOH intake in the used paradigm. Conclusions The results provide further evidence for the role of accumbens shell μ‐opioid receptors but not κ‐opioid receptors in mediating reinforcing effects of EtOH and in regulating EtOH consumption. The results also provide support for views suggesting that the nucleus accumbens shell has a major role in mediating EtOH reward. The opioidergic system has been implicated in the control of ethanol (EtOH) intake and reward. However, the exact mechanisms of opioidergic involvement remain to be elucidated. In this study, alcohol‐preferring AA rats received intra‐accumbal microinfusions of drugs acting on μ‐ and κ‐opioid receptors and their effects on acute EtOH intake were monitored. The μ‐opioid receptor antagonist CTOP increased and agonist DAMGO tended to decrease EtOH intake. The results suggest that accumbal μ‐ but not κ‐opioid receptors participate in controlling EtOH intake.