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Ethanol drinking experience attenuates (-)sulpiride-induced increases in extracellular dopamine levels in the nucleus accumbens of alcohol-preferring (P) rats.
Alcohol Clin Exp Res. 2003 Mar; 27(3):424-31.AC

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 D(2) 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 D(2) 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 microl/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 microM 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 microM 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 microM 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 D(2) autoreceptors in the NAc of P rats.

Authors+Show Affiliations

Department of Psychology, Purdue School of Science, 402 N. Blackford Street, IUPUI, Indianapolis, IN 46202-3275, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

12658107

Citation

Engleman, Eric A., et al. "Ethanol Drinking Experience Attenuates (-)sulpiride-induced Increases in Extracellular Dopamine Levels in the Nucleus Accumbens of Alcohol-preferring (P) Rats." Alcoholism, Clinical and Experimental Research, vol. 27, no. 3, 2003, pp. 424-31.
Engleman EA, McBride WJ, Li TK, et al. Ethanol drinking experience attenuates (-)sulpiride-induced increases in extracellular dopamine levels in the nucleus accumbens of alcohol-preferring (P) rats. Alcohol Clin Exp Res. 2003;27(3):424-31.
Engleman, E. A., McBride, W. J., Li, T. K., Lumeng, L., & Murphy, J. M. (2003). Ethanol drinking experience attenuates (-)sulpiride-induced increases in extracellular dopamine levels in the nucleus accumbens of alcohol-preferring (P) rats. Alcoholism, Clinical and Experimental Research, 27(3), 424-31.
Engleman EA, et al. Ethanol Drinking Experience Attenuates (-)sulpiride-induced Increases in Extracellular Dopamine Levels in the Nucleus Accumbens of Alcohol-preferring (P) Rats. Alcohol Clin Exp Res. 2003;27(3):424-31. PubMed PMID: 12658107.
* Article titles in AMA citation format should be in sentence-case
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 A, AU - McBride,William J, AU - Li,Ting-Kai, AU - Lumeng,Lawrence, AU - Murphy,James M, PY - 2003/3/27/pubmed PY - 2003/9/25/medline PY - 2003/3/27/entrez SP - 424 EP - 31 JF - Alcoholism, clinical and experimental research JO - Alcohol Clin Exp Res VL - 27 IS - 3 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 D(2) 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 D(2) 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 microl/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 microM 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 microM 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 microM 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 D(2) autoreceptors in the NAc of P rats. SN - 0145-6008 UR - https://www.unboundmedicine.com/medline/citation/12658107/Ethanol_drinking_experience_attenuates____sulpiride_induced_increases_in_extracellular_dopamine_levels_in_the_nucleus_accumbens_of_alcohol_preferring__P__rats_ L2 - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&amp;PAGE=linkout&amp;SEARCH=12658107.ui DB - PRIME DP - Unbound Medicine ER -