Accumbal µ-opioid receptors modulate ethanol intake in alcohol-preferring Alko Alcohol rats

Research output: Contribution to journalArticleScientificpeer-review

Abstract

BackgroundThe nucleus accumbens shell is a key brain area mediating the reinforcing effects of ethanol (EtOH). Previously, it has been shown that the density of -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 - and -opioid receptors in controlling EtOH intake in alcohol-preferring AA rats.

MethodsMicroinfusions of the -opioid receptor antagonist CTOP (0.3 and 1g/site), -opioid receptor agonist DAMGO (0.03 and 0.1g/site), nonselective opioid receptor agonist morphine (30g/site), and -opioid receptor agonist U50488H (0.3 and 1g/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.

ResultsCTOP (1g/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.

ConclusionsThe results provide further evidence for the role of accumbens shell -opioid receptors but not -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.
Original languageEnglish
JournalAlcoholism: Clinical and Experimental Research
Volume40
Issue number10
Pages (from-to)2114-2123
Number of pages10
ISSN0145-6008
DOIs
Publication statusPublished - Oct 2016
MoE publication typeA1 Journal article-refereed

Fields of Science

  • 317 Pharmacy
  • Nucleus Accumbens Shell
  • mu-Opioid Receptor
  • kappa-Opioid Receptor
  • Ethanol Intake
  • Alko Alcohol Rat
  • AVOIDING ANA RATS
  • NUCLEUS-ACCUMBENS
  • VENTRAL PALLIDUM
  • MICRODIALYSIS PROFILE
  • AGONIST U50,488H
  • WISTAR RATS
  • DRINKING
  • REWARD
  • AA
  • RELEASE

Cite this

@article{13d58c36a3974827b9a71855ea624f76,
title = "Accumbal µ-opioid receptors modulate ethanol intake in alcohol-preferring Alko Alcohol rats",
abstract = "BackgroundThe nucleus accumbens shell is a key brain area mediating the reinforcing effects of ethanol (EtOH). Previously, it has been shown that the density of -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 - and -opioid receptors in controlling EtOH intake in alcohol-preferring AA rats.MethodsMicroinfusions of the -opioid receptor antagonist CTOP (0.3 and 1g/site), -opioid receptor agonist DAMGO (0.03 and 0.1g/site), nonselective opioid receptor agonist morphine (30g/site), and -opioid receptor agonist U50488H (0.3 and 1g/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.ResultsCTOP (1g/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.ConclusionsThe results provide further evidence for the role of accumbens shell -opioid receptors but not -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.",
keywords = "317 Pharmacy, Nucleus Accumbens Shell , mu-Opioid Receptor , kappa-Opioid Receptor , Ethanol Intake , Alko Alcohol Rat , AVOIDING ANA RATS , NUCLEUS-ACCUMBENS , VENTRAL PALLIDUM , MICRODIALYSIS PROFILE , AGONIST U50,488H , WISTAR RATS , DRINKING , REWARD , AA , RELEASE",
author = "Uhari-V{\"a}{\"a}n{\"a}nen, {Johanna Kristiina} and Raasmaja, {Atso Ilari} and Pia B{\"a}ckstr{\"o}m and Ville Oinio and Airavaara, {Mikko Tuomas} and Petteri Piepponen and Kalervo Kiianmaa",
note = "Supported by the Finnish Foundation for Alcohol Studies Volume: Proceeding volume:",
year = "2016",
month = "10",
doi = "10.1111/acer.13176",
language = "English",
volume = "40",
pages = "2114--2123",
journal = "Alcoholism: Clinical and Experimental Research",
issn = "0145-6008",
publisher = "Wiley",
number = "10",

}

TY - JOUR

T1 - Accumbal µ-opioid receptors modulate ethanol intake in alcohol-preferring Alko Alcohol rats

AU - Uhari-Väänänen, Johanna Kristiina

AU - Raasmaja, Atso Ilari

AU - Bäckström, Pia

AU - Oinio, Ville

AU - Airavaara, Mikko Tuomas

AU - Piepponen, Petteri

AU - Kiianmaa, Kalervo

N1 - Supported by the Finnish Foundation for Alcohol Studies Volume: Proceeding volume:

PY - 2016/10

Y1 - 2016/10

N2 - BackgroundThe nucleus accumbens shell is a key brain area mediating the reinforcing effects of ethanol (EtOH). Previously, it has been shown that the density of -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 - and -opioid receptors in controlling EtOH intake in alcohol-preferring AA rats.MethodsMicroinfusions of the -opioid receptor antagonist CTOP (0.3 and 1g/site), -opioid receptor agonist DAMGO (0.03 and 0.1g/site), nonselective opioid receptor agonist morphine (30g/site), and -opioid receptor agonist U50488H (0.3 and 1g/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.ResultsCTOP (1g/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.ConclusionsThe results provide further evidence for the role of accumbens shell -opioid receptors but not -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.

AB - BackgroundThe nucleus accumbens shell is a key brain area mediating the reinforcing effects of ethanol (EtOH). Previously, it has been shown that the density of -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 - and -opioid receptors in controlling EtOH intake in alcohol-preferring AA rats.MethodsMicroinfusions of the -opioid receptor antagonist CTOP (0.3 and 1g/site), -opioid receptor agonist DAMGO (0.03 and 0.1g/site), nonselective opioid receptor agonist morphine (30g/site), and -opioid receptor agonist U50488H (0.3 and 1g/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.ResultsCTOP (1g/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.ConclusionsThe results provide further evidence for the role of accumbens shell -opioid receptors but not -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.

KW - 317 Pharmacy

KW - Nucleus Accumbens Shell

KW - mu-Opioid Receptor

KW - kappa-Opioid Receptor

KW - Ethanol Intake

KW - Alko Alcohol Rat

KW - AVOIDING ANA RATS

KW - NUCLEUS-ACCUMBENS

KW - VENTRAL PALLIDUM

KW - MICRODIALYSIS PROFILE

KW - AGONIST U50,488H

KW - WISTAR RATS

KW - DRINKING

KW - REWARD

KW - AA

KW - RELEASE

U2 - 10.1111/acer.13176

DO - 10.1111/acer.13176

M3 - Article

VL - 40

SP - 2114

EP - 2123

JO - Alcoholism: Clinical and Experimental Research

JF - Alcoholism: Clinical and Experimental Research

SN - 0145-6008

IS - 10

ER -