Effects of a range of dopamine receptor agonists and antagonists on ethanol intake in the rat

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The aim of this study was to assess the effects of a range of dopaminergic agents on consumption of an ethanol solution (10% ethanol, 3% glucose) in rats. A two-bottle, free-choice paradigm was used following induction of ethanol consumption and preference in standard laboratory rats. The model used provides a robust and reliable level of ethanol oral administration in normal laboratory rats. Both ethanol intake and preference were reduced by a dopamine D 1 receptor partial agonist, SFK 38393 ((±)-1-phenyl-2,3,4,5-tetrahydro-(1 H)-3-benzazepine-7,8-diol hydrochloride), in a dose-dependent manner. The dopamine D 2/D 3 receptor agonist 7-OH-DPAT ((±)-7-hydroxy- N,N-(di- n-propyl-2-aminotetralin)) at the lowest dose of 0.01 mg/kg increased both ethanol intake and preference. At higher doses (0.03–0.1 mg/kg) no significant effects were found. The dopamine D 1 receptor antagonist SCH 23390 ( R-(+)-7-chloro-2,3,4,5-tetrahydro-3-methyl-1-phenyl-1 H-3-3benzazepine-8-ol), dopamine D 2/D 3 receptor antagonist raclopride and 5-HT 2/D 2 receptor antagonist risperidone did not affect ethanol consumption, although all at high doses induced a significant decrease in water intake, indicating a non-specific decrease in consummatory behavior with these compounds. These results suggest the involvement of the dopaminergic system in ethanol intake and ethanol reinforcement with dopamine D 1 and D 2/D 3 receptors playing opposing roles. Blockade of dopamine D 2 receptors had no selective effect on ethanol consumption and ethanol preference.