title: Accumbal μ-Opioid Receptors Modulate Ethanol Intake in Alcohol-Preferring Alko Alcohol Rats.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors: Department of Health, National Institute for Health and Welfare, Helsinki, Finland. johanna.uhari@helsinki.fi.|Department of Pharmacology and Pharmacotherapy, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland. johanna.uhari@helsinki.fi.
authors: Johanna
authors: J
authors: Uhari-Väänänen
authors: Department of Pharmacology and Pharmacotherapy, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
authors: Atso
authors: A
authors: Raasmaja
authors: Department of Health, National Institute for Health and Welfare, Helsinki, Finland.
authors: Pia
authors: P
authors: Bäckström
authors: Department of Health, National Institute for Health and Welfare, Helsinki, Finland.|Department of Pharmacology and Pharmacotherapy, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
authors: Ville
authors: V
authors: Oinio
authors: Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
authors: Mikko
authors: M
authors: Airavaara
authors: Department of Pharmacology and Pharmacotherapy, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
authors: Petteri
authors: P
authors: Piepponen
authors: Department of Health, National Institute for Health and Welfare, Helsinki, Finland.
authors: Kalervo
authors: K
authors: Kiianmaa
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology; D000428:Alcohol Drinking / Q000503:physiopathology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000008:administration & dosage / Q000494:pharmacology; D000431:Ethanol / Q000008:administration & dosage*; D008297:Male; D008845:Microinjections; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000502:physiology*; D051381:Rats; D017473:Receptors, Opioid, kappa / Q000819:agonists / Q000502:physiology*; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D012201:Reward; D013004:Somatostatin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D013045:Species Specificity
chemical_list: D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C049352:phenylalanyl-cyclo(cysteinyltyrosyl-tryptophyl-ornithyl-threonyl-penicillamine)threoninamide; D000431:Ethanol; D013004:Somatostatin; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine
keywords: Alko Alcohol Rat; Ethanol Intake; Nucleus Accumbens Shell; κ-Opioid Receptor; μ-Opioid Receptor