Tolcapone Suppresses Ethanol Intake in Alcohol-Preferring Rats Performing a Novel Cued Access Protocol

Aqilah M. Mccane, Cristine L. Czachowski, Christopher C. Lapish

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background: Dopamine (DA) has been shown to play a central role in regulating motivated behavior and encoding reward. Chronic drug abuse elicits a state of hypodopaminergia in the mesocorticolimbic (MCL) system in both humans and preclinical rodent models of addiction, including those modeling alcohol use disorders (AUD). Methods: Working under the hypothesis that reductions in the bioavailability of DA play an integral role in the expression of the excessive drinking phenotype, the catechol-O-methyltransferase (COMT) inhibitor tolcapone was used as a means to amplify cortical DA concentration and drinking behaviors were then assessed. Sucrose and ethanol (EtOH) consumption were measured in P and Wistar rats in both a free choice drinking protocol and a novel cued access protocol. Results: Tolcapone attenuated the consumption of EtOH, and to a lesser extent sucrose, in P rats in the cued access protocol, while no effect was observed in the free choice drinking protocol. Tolcapone also decreased EtOH consumption in high drinking Wistar rats. A follow-up experiment using the indirect DA agonist d-amphetamine showed no change in EtOH consumption. Conclusions: Collectively, these data suggest that COMT inhibitors may be capable of alleviating the extremely motivating or salient nature of stimuli associated with alcohol. The hypothesis is put forth that the relative specificity of tolcapone for cortical DA systems may mediate the suppression of the high seeking/drinking phenotype.

Original languageEnglish (US)
Pages (from-to)2468-2478
Number of pages11
JournalAlcoholism: Clinical and Experimental Research
Volume38
Issue number9
DOIs
StatePublished - 2014

Fingerprint

Drinking
Rats
Dopamine
Ethanol
Alcohols
Sucrose
Wistar Rats
Dextroamphetamine
Dopamine Agonists
Phenotype
Drinking Behavior
Reward
Biological Availability
Substance-Related Disorders
Rodentia
tolcapone
Pharmaceutical Preparations
Experiments
Catechol O-Methyltransferase Inhibitors

Keywords

  • Alcohol preferring rat
  • Catechol-O-Methyltransferase
  • Dopamine
  • Prefrontal cortex
  • Tolcapone

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Psychiatry and Mental health
  • Toxicology

Cite this

Tolcapone Suppresses Ethanol Intake in Alcohol-Preferring Rats Performing a Novel Cued Access Protocol. / Mccane, Aqilah M.; Czachowski, Cristine L.; Lapish, Christopher C.

In: Alcoholism: Clinical and Experimental Research, Vol. 38, No. 9, 2014, p. 2468-2478.

Research output: Contribution to journalArticle

Mccane, Aqilah M. ; Czachowski, Cristine L. ; Lapish, Christopher C. / Tolcapone Suppresses Ethanol Intake in Alcohol-Preferring Rats Performing a Novel Cued Access Protocol. In: Alcoholism: Clinical and Experimental Research. 2014 ; Vol. 38, No. 9. pp. 2468-2478.
@article{4164bdeb8a744d64afdb0cf04e6d38cd,
title = "Tolcapone Suppresses Ethanol Intake in Alcohol-Preferring Rats Performing a Novel Cued Access Protocol",
abstract = "Background: Dopamine (DA) has been shown to play a central role in regulating motivated behavior and encoding reward. Chronic drug abuse elicits a state of hypodopaminergia in the mesocorticolimbic (MCL) system in both humans and preclinical rodent models of addiction, including those modeling alcohol use disorders (AUD). Methods: Working under the hypothesis that reductions in the bioavailability of DA play an integral role in the expression of the excessive drinking phenotype, the catechol-O-methyltransferase (COMT) inhibitor tolcapone was used as a means to amplify cortical DA concentration and drinking behaviors were then assessed. Sucrose and ethanol (EtOH) consumption were measured in P and Wistar rats in both a free choice drinking protocol and a novel cued access protocol. Results: Tolcapone attenuated the consumption of EtOH, and to a lesser extent sucrose, in P rats in the cued access protocol, while no effect was observed in the free choice drinking protocol. Tolcapone also decreased EtOH consumption in high drinking Wistar rats. A follow-up experiment using the indirect DA agonist d-amphetamine showed no change in EtOH consumption. Conclusions: Collectively, these data suggest that COMT inhibitors may be capable of alleviating the extremely motivating or salient nature of stimuli associated with alcohol. The hypothesis is put forth that the relative specificity of tolcapone for cortical DA systems may mediate the suppression of the high seeking/drinking phenotype.",
keywords = "Alcohol preferring rat, Catechol-O-Methyltransferase, Dopamine, Prefrontal cortex, Tolcapone",
author = "Mccane, {Aqilah M.} and Czachowski, {Cristine L.} and Lapish, {Christopher C.}",
year = "2014",
doi = "10.1111/acer.12515",
language = "English (US)",
volume = "38",
pages = "2468--2478",
journal = "Alcoholism: Clinical and Experimental Research",
issn = "0145-6008",
publisher = "Wiley-Blackwell",
number = "9",

}

TY - JOUR

T1 - Tolcapone Suppresses Ethanol Intake in Alcohol-Preferring Rats Performing a Novel Cued Access Protocol

AU - Mccane, Aqilah M.

AU - Czachowski, Cristine L.

AU - Lapish, Christopher C.

PY - 2014

Y1 - 2014

N2 - Background: Dopamine (DA) has been shown to play a central role in regulating motivated behavior and encoding reward. Chronic drug abuse elicits a state of hypodopaminergia in the mesocorticolimbic (MCL) system in both humans and preclinical rodent models of addiction, including those modeling alcohol use disorders (AUD). Methods: Working under the hypothesis that reductions in the bioavailability of DA play an integral role in the expression of the excessive drinking phenotype, the catechol-O-methyltransferase (COMT) inhibitor tolcapone was used as a means to amplify cortical DA concentration and drinking behaviors were then assessed. Sucrose and ethanol (EtOH) consumption were measured in P and Wistar rats in both a free choice drinking protocol and a novel cued access protocol. Results: Tolcapone attenuated the consumption of EtOH, and to a lesser extent sucrose, in P rats in the cued access protocol, while no effect was observed in the free choice drinking protocol. Tolcapone also decreased EtOH consumption in high drinking Wistar rats. A follow-up experiment using the indirect DA agonist d-amphetamine showed no change in EtOH consumption. Conclusions: Collectively, these data suggest that COMT inhibitors may be capable of alleviating the extremely motivating or salient nature of stimuli associated with alcohol. The hypothesis is put forth that the relative specificity of tolcapone for cortical DA systems may mediate the suppression of the high seeking/drinking phenotype.

AB - Background: Dopamine (DA) has been shown to play a central role in regulating motivated behavior and encoding reward. Chronic drug abuse elicits a state of hypodopaminergia in the mesocorticolimbic (MCL) system in both humans and preclinical rodent models of addiction, including those modeling alcohol use disorders (AUD). Methods: Working under the hypothesis that reductions in the bioavailability of DA play an integral role in the expression of the excessive drinking phenotype, the catechol-O-methyltransferase (COMT) inhibitor tolcapone was used as a means to amplify cortical DA concentration and drinking behaviors were then assessed. Sucrose and ethanol (EtOH) consumption were measured in P and Wistar rats in both a free choice drinking protocol and a novel cued access protocol. Results: Tolcapone attenuated the consumption of EtOH, and to a lesser extent sucrose, in P rats in the cued access protocol, while no effect was observed in the free choice drinking protocol. Tolcapone also decreased EtOH consumption in high drinking Wistar rats. A follow-up experiment using the indirect DA agonist d-amphetamine showed no change in EtOH consumption. Conclusions: Collectively, these data suggest that COMT inhibitors may be capable of alleviating the extremely motivating or salient nature of stimuli associated with alcohol. The hypothesis is put forth that the relative specificity of tolcapone for cortical DA systems may mediate the suppression of the high seeking/drinking phenotype.

KW - Alcohol preferring rat

KW - Catechol-O-Methyltransferase

KW - Dopamine

KW - Prefrontal cortex

KW - Tolcapone

UR - http://www.scopus.com/inward/record.url?scp=84925957008&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84925957008&partnerID=8YFLogxK

U2 - 10.1111/acer.12515

DO - 10.1111/acer.12515

M3 - Article

AN - SCOPUS:84925957008

VL - 38

SP - 2468

EP - 2478

JO - Alcoholism: Clinical and Experimental Research

JF - Alcoholism: Clinical and Experimental Research

SN - 0145-6008

IS - 9

ER -