Ethanol drinking experience attenuates (-)sulpiride-induced increases in extracellular dopamine levels in the nucleus accumbens of alcohol-preferring (P) rats

Eric Engleman, William J. McBride, Ting Kai Li, Lawrence Lumeng, James M. Murphy

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Background: The reinforcing properties of ethanol may be partly mediated through the mesolimbic dopamine (DA) system. This study examines the effects of local application of the DA D2 receptor antagonist (-)sulpiride (SUL) on ethanol drinking of alcohol-preferring (P) rats, and extracellular DA levels in the nucleus accumbens (NAc) of P rats that were either ethanol-naive or had been chronically drinking ethanol. Methods: Microdialysis was used to sample NAc DA levels, and reverse microdialysis was used to locally administer the D2 antagonist (-)sulpiride (SUL) into the NAc of adult female P rats that were either drinking ethanol (n = 17) or were ethanol-naive (n = 24). Stable intake of 15% (v/v) ethanol (≥0.75 g/kg) was established for the ethanol-drinking group in daily 1-hr access periods over a minimum of 4 weeks before surgery. Naive and ethanol-drinking rats were implanted with bilateral guide cannulae aimed 4 mm above the NAc shell. After recovery from surgery, microdialysis probes (active area = 2 mm) were inserted bilaterally into the NAc. Two days later, rats in the ethanol-drinking and naive groups were each divided into two groups; one group was bilaterally perfused (1.0 μl/min) with artificial cerebrospinal fluid (aCSF) and the other group was further divided into three subgroups that were perfused with aCSF + either 50, 100, or 200 μM SUL for 240 min. During the last 60 min of perfusion, the ethanol-drinking rats were given their daily 1-hr ethanol access period. Following ethanol access, the aCSF + SUL subgroups were then given aCSF only. The entire perfusion procedure was repeated 24 hr later, but the aCSF only and aCSF + SUL group treatment conditions were transposed. Results: In ethanol-drinking rats, 100 and 200 μM SUL increased extracellular NAc DA levels to approximately 200% of basal values, but did not significantly alter ethanol intake. In ethanol-naive P rats, 100 and 200 μM SUL increased extracellular NAc DA levels significantly more (450% of basal; p < 0.05) than in the ethanol-drinking group. Conclusions: The findings are consistent with the hypothesis that ethanol-drinking experience causes a desensitization or a down-regulation of D2 autoreceptors in the NAc of P rats.

Original languageEnglish
Pages (from-to)424-431
Number of pages8
JournalAlcoholism: Clinical and Experimental Research
Volume27
Issue number3
DOIs
StatePublished - Mar 1 2003

Fingerprint

Sulpiride
Nucleus Accumbens
Drinking
Rats
Dopamine
Ethanol
Alcohols
Cerebrospinal fluid
Cerebrospinal Fluid
Microdialysis
Surgery
Perfusion
Autoreceptors

Keywords

  • Alcohol Drinking
  • Alcoholism
  • Dopamine
  • Microdialysis
  • Reinforcement

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology

Cite this

Ethanol drinking experience attenuates (-)sulpiride-induced increases in extracellular dopamine levels in the nucleus accumbens of alcohol-preferring (P) rats. / Engleman, Eric; McBride, William J.; Li, Ting Kai; Lumeng, Lawrence; Murphy, James M.

In: Alcoholism: Clinical and Experimental Research, Vol. 27, No. 3, 01.03.2003, p. 424-431.

Research output: Contribution to journalArticle

@article{b5fdca0ebdf34dd4a63444422367682b,
title = "Ethanol drinking experience attenuates (-)sulpiride-induced increases in extracellular dopamine levels in the nucleus accumbens of alcohol-preferring (P) rats",
abstract = "Background: The reinforcing properties of ethanol may be partly mediated through the mesolimbic dopamine (DA) system. This study examines the effects of local application of the DA D2 receptor antagonist (-)sulpiride (SUL) on ethanol drinking of alcohol-preferring (P) rats, and extracellular DA levels in the nucleus accumbens (NAc) of P rats that were either ethanol-naive or had been chronically drinking ethanol. Methods: Microdialysis was used to sample NAc DA levels, and reverse microdialysis was used to locally administer the D2 antagonist (-)sulpiride (SUL) into the NAc of adult female P rats that were either drinking ethanol (n = 17) or were ethanol-naive (n = 24). Stable intake of 15{\%} (v/v) ethanol (≥0.75 g/kg) was established for the ethanol-drinking group in daily 1-hr access periods over a minimum of 4 weeks before surgery. Naive and ethanol-drinking rats were implanted with bilateral guide cannulae aimed 4 mm above the NAc shell. After recovery from surgery, microdialysis probes (active area = 2 mm) were inserted bilaterally into the NAc. Two days later, rats in the ethanol-drinking and naive groups were each divided into two groups; one group was bilaterally perfused (1.0 μl/min) with artificial cerebrospinal fluid (aCSF) and the other group was further divided into three subgroups that were perfused with aCSF + either 50, 100, or 200 μM SUL for 240 min. During the last 60 min of perfusion, the ethanol-drinking rats were given their daily 1-hr ethanol access period. Following ethanol access, the aCSF + SUL subgroups were then given aCSF only. The entire perfusion procedure was repeated 24 hr later, but the aCSF only and aCSF + SUL group treatment conditions were transposed. Results: In ethanol-drinking rats, 100 and 200 μM SUL increased extracellular NAc DA levels to approximately 200{\%} of basal values, but did not significantly alter ethanol intake. In ethanol-naive P rats, 100 and 200 μM SUL increased extracellular NAc DA levels significantly more (450{\%} of basal; p < 0.05) than in the ethanol-drinking group. Conclusions: The findings are consistent with the hypothesis that ethanol-drinking experience causes a desensitization or a down-regulation of D2 autoreceptors in the NAc of P rats.",
keywords = "Alcohol Drinking, Alcoholism, Dopamine, Microdialysis, Reinforcement",
author = "Eric Engleman and McBride, {William J.} and Li, {Ting Kai} and Lawrence Lumeng and Murphy, {James M.}",
year = "2003",
month = "3",
day = "1",
doi = "10.1097/01.ALC.0000056618.57931.A5",
language = "English",
volume = "27",
pages = "424--431",
journal = "Alcoholism: Clinical and Experimental Research",
issn = "0145-6008",
publisher = "Wiley-Blackwell",
number = "3",

}

TY - JOUR

T1 - Ethanol drinking experience attenuates (-)sulpiride-induced increases in extracellular dopamine levels in the nucleus accumbens of alcohol-preferring (P) rats

AU - Engleman, Eric

AU - McBride, William J.

AU - Li, Ting Kai

AU - Lumeng, Lawrence

AU - Murphy, James M.

PY - 2003/3/1

Y1 - 2003/3/1

N2 - Background: The reinforcing properties of ethanol may be partly mediated through the mesolimbic dopamine (DA) system. This study examines the effects of local application of the DA D2 receptor antagonist (-)sulpiride (SUL) on ethanol drinking of alcohol-preferring (P) rats, and extracellular DA levels in the nucleus accumbens (NAc) of P rats that were either ethanol-naive or had been chronically drinking ethanol. Methods: Microdialysis was used to sample NAc DA levels, and reverse microdialysis was used to locally administer the D2 antagonist (-)sulpiride (SUL) into the NAc of adult female P rats that were either drinking ethanol (n = 17) or were ethanol-naive (n = 24). Stable intake of 15% (v/v) ethanol (≥0.75 g/kg) was established for the ethanol-drinking group in daily 1-hr access periods over a minimum of 4 weeks before surgery. Naive and ethanol-drinking rats were implanted with bilateral guide cannulae aimed 4 mm above the NAc shell. After recovery from surgery, microdialysis probes (active area = 2 mm) were inserted bilaterally into the NAc. Two days later, rats in the ethanol-drinking and naive groups were each divided into two groups; one group was bilaterally perfused (1.0 μl/min) with artificial cerebrospinal fluid (aCSF) and the other group was further divided into three subgroups that were perfused with aCSF + either 50, 100, or 200 μM SUL for 240 min. During the last 60 min of perfusion, the ethanol-drinking rats were given their daily 1-hr ethanol access period. Following ethanol access, the aCSF + SUL subgroups were then given aCSF only. The entire perfusion procedure was repeated 24 hr later, but the aCSF only and aCSF + SUL group treatment conditions were transposed. Results: In ethanol-drinking rats, 100 and 200 μM SUL increased extracellular NAc DA levels to approximately 200% of basal values, but did not significantly alter ethanol intake. In ethanol-naive P rats, 100 and 200 μM SUL increased extracellular NAc DA levels significantly more (450% of basal; p < 0.05) than in the ethanol-drinking group. Conclusions: The findings are consistent with the hypothesis that ethanol-drinking experience causes a desensitization or a down-regulation of D2 autoreceptors in the NAc of P rats.

AB - Background: The reinforcing properties of ethanol may be partly mediated through the mesolimbic dopamine (DA) system. This study examines the effects of local application of the DA D2 receptor antagonist (-)sulpiride (SUL) on ethanol drinking of alcohol-preferring (P) rats, and extracellular DA levels in the nucleus accumbens (NAc) of P rats that were either ethanol-naive or had been chronically drinking ethanol. Methods: Microdialysis was used to sample NAc DA levels, and reverse microdialysis was used to locally administer the D2 antagonist (-)sulpiride (SUL) into the NAc of adult female P rats that were either drinking ethanol (n = 17) or were ethanol-naive (n = 24). Stable intake of 15% (v/v) ethanol (≥0.75 g/kg) was established for the ethanol-drinking group in daily 1-hr access periods over a minimum of 4 weeks before surgery. Naive and ethanol-drinking rats were implanted with bilateral guide cannulae aimed 4 mm above the NAc shell. After recovery from surgery, microdialysis probes (active area = 2 mm) were inserted bilaterally into the NAc. Two days later, rats in the ethanol-drinking and naive groups were each divided into two groups; one group was bilaterally perfused (1.0 μl/min) with artificial cerebrospinal fluid (aCSF) and the other group was further divided into three subgroups that were perfused with aCSF + either 50, 100, or 200 μM SUL for 240 min. During the last 60 min of perfusion, the ethanol-drinking rats were given their daily 1-hr ethanol access period. Following ethanol access, the aCSF + SUL subgroups were then given aCSF only. The entire perfusion procedure was repeated 24 hr later, but the aCSF only and aCSF + SUL group treatment conditions were transposed. Results: In ethanol-drinking rats, 100 and 200 μM SUL increased extracellular NAc DA levels to approximately 200% of basal values, but did not significantly alter ethanol intake. In ethanol-naive P rats, 100 and 200 μM SUL increased extracellular NAc DA levels significantly more (450% of basal; p < 0.05) than in the ethanol-drinking group. Conclusions: The findings are consistent with the hypothesis that ethanol-drinking experience causes a desensitization or a down-regulation of D2 autoreceptors in the NAc of P rats.

KW - Alcohol Drinking

KW - Alcoholism

KW - Dopamine

KW - Microdialysis

KW - Reinforcement

UR - http://www.scopus.com/inward/record.url?scp=0037345656&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037345656&partnerID=8YFLogxK

U2 - 10.1097/01.ALC.0000056618.57931.A5

DO - 10.1097/01.ALC.0000056618.57931.A5

M3 - Article

C2 - 12658107

AN - SCOPUS:0037345656

VL - 27

SP - 424

EP - 431

JO - Alcoholism: Clinical and Experimental Research

JF - Alcoholism: Clinical and Experimental Research

SN - 0145-6008

IS - 3

ER -