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NEUROPHARMACOLOGY

Ethanol Drinking and Deprivation Alter Dopaminergic and Serotonergic Function in the Nucleus Accumbens of Alcohol-Preferring Rats

Departments of Psychiatry (R.J.T., E.A.E., Z.A.R., J.M.M., W.J.M.), Medicine (L.L., T.-K.L.), and Biochemistry and Molecular Biology (R.J.T., L.L., W.J.M.), Institute of Psychiatric Research (R.J.T., E.A.E., Z.A.R., J.M.M., W.J.M.), Indiana University School of Medicine, Indianapolis, Indiana; Department of Psychology, Purdue School of Science, Indiana University-Purdue University Indianapolis (E.A.E., J.M.M.), Indianapolis, Indiana; and Veterans Affairs Medical Center (L.L.), Indianapolis, Indiana

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.

Address correspondence to: Dr. Richard J. Thielen, Department of Psychiatry, Institute of Psychiatric Research, Indiana University Medical Center, 791 Union Dr., Indianapolis, IN 46202-4887. E-mail: rthielen{at}iupui.edu

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