Dopamine release in the nucleus accumbens (shell) of two lines of rats selectively bred to prefer or avoid ethanol.
Lower tissue levels of dopamine and 5-hydroxytryptamine (5-HT) have been found in the nucleus accumbens of alcohol-naïve rats selectively bred to prefer ethanol than in rats bred to avoid it. These findings have led to the hypothesis that differences in the dopamine and 5-HT tone may be linked to ethanol preference. In the present study we used the in vivo microdialysis technique to determine the actual extracellular levels of dopamine, its metabolites 3,4-dihydroxyphenyl acetaldehyde (DOPALD), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-HT and 5-hydroxyindolacetic acid (5-HIAA) in the shell of nucleus accumbens of rat lines selectively bred as either high-ethanol (UChB) or low-ethanol (UChA) drinkers. Basal extracellular levels of dopamine, DOPALD, DOPAC and HVA were lower in the shell of nucleus accumbens of ethanol-naïve UChB than in UChA rats. In agreement, when perfused with 100 microM d-amphetamine or 100 mM KCl lower dopamine increases were observed in nucleus accumbens of UChB rats compared to UChA rats, indicating lower cytosolic (d-amphetamine releasable) and vesicular (KCl releasable) dopamine pools in UChB animals. Since the experiments were performed in ethanol-naïve rats, the present results suggest an innate deficiency in the mesolimbic dopamine system of UChB rats. There were no line differences in basal, d-amphetamine or KCl stimulated 5-HT levels. Thus, the present findings support a role of dopamine, but not of 5-HT, as predictor of ethanol preference in UChB rats. Overall, data obtained are in agreement with previous reports in other rat lines showing that lower dopamine levels and its metabolites are associated with a genetic predisposition to ethanol preference.
Quintanilla
María Elena
ME
Programme of Molecular & Clinical Pharmacology, ICBM, Faculty of Medicine; PO Box 70,000 Santiago 7, Chile. equintanilla@med.uchile.cl
Bustamante
Diego
D
Tampier
Lutske
L
Israel
Yedy
Y
Herrera-Marschitz
Mario
M
D015102:3,4-Dihydroxyphenylacetic Acid / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism; D000428:Alcohol Drinking / Q000235:genetics / Q000503:physiopathology*; D000437:Alcoholism / Q000235:genetics / Q000517:prevention & control*; D000769:Anesthesia, Inhalation; D000818:Animals; D001947:Breeding / Q000379:methods; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003913:Dextroamphetamine / Q000008:administration & dosage / Q000494:pharmacology; D004298:Dopamine / Q000032:analysis / Q000378:metabolism*; D005260:Female; D020022:Genetic Predisposition to Disease; D006719:Homovanillic Acid / Q000032:analysis / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000032:analysis / Q000378:metabolism; D007530:Isoflurane / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D017551:Microdialysis / Q000379:methods; D009714:Nucleus Accumbens / Q000378:metabolism*; D011189:Potassium Chloride / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000032:analysis / Q000378:metabolism; D013238:Stereotaxic Techniques
D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; C007430:3,4-dihydroxyphenylacetaldehyde; D011189:Potassium Chloride; D007530:Isoflurane; D003913:Dextroamphetamine; D004298:Dopamine; D006719:Homovanillic Acid