Abstract
The alcohol deprivation effect is a temporary increase in the intake of, or preference for, ethanol after a period of deprivation that may result from persistent changes in key limbic regions thought to regulate alcohol drinking, such as the nucleus accumbens. The present study tested the hypothesis that chronic alcohol drinking under continuous 24-h free-choice conditions alters dopamine and serotonin neurotransmission in the nucleus accumbens and that these alterations persist in the absence of alcohol. Using the no-net-flux microdialysis method, the steady-state extracellular concentration (point of no-netflux) for dopamine was approximately 25% higher in the adult female alcohol-preferring P rats given prior access to 10% ethanol, even after 2 weeks of ethanol abstinence, compared with the P rats gives access only to water. However, the extracellular concentration of serotonin was approximately 35% lower in animals given 8 weeks of continuous access to ethanol compared with water controls and animals deprived of ethanol for 2 weeks. The effect of local perfusion with 100 μM sulpiride (D2 receptor antagonist) and 35 μM 1-(m-chlorophenyl)-biguanide (5-hydroxytryptamine3 receptor agonist) on dopamine overflow were reduced approximately 33% in both groups of ethanol-exposed P rats compared with water controls. Free-choice alcohol drinking by P rats alters dopamine and serotonin neurotransmission in the nucleus accumbens, and many of these effects persist for at least 2 weeks in the absence of ethanol, suggesting that these underlying persistent changes may be in part responsible for increased ethanol drinking observed in the alcohol-deprivation effect.
Footnotes
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This study was supported in part by National Institute on Alcohol Abuse and Alcoholism Grants AA07611, AA11261, and AA10717.
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Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
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DOI: 10.1124/jpet.103.059790.
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ABBREVIATIONS: 5-HT, 5-hydroxytryptamine; P, alcohol-preferring; Ed, extraction fraction; ACSF, artificial cerebral spinal fluid; HPLC, high-performance liquid chromatography; CPBG, 1-(m-chlorophenyl)-biguanide; ANOVA, analysis of variance; AUC, area under the curve.
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↵1 Current address: National Institute on Alcohol Abuse and Alcoholism, The Willco Bldg., 6000 Executive Blvd., Suite 400, Bethesda, MD 10892-7003.
- Received September 17, 2003.
- Accepted December 4, 2003.
- The American Society for Pharmacology and Experimental Therapeutics
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