title: Dopamine D3 receptor antagonist effects on the motivational effects of ethanol.
abstract: Dopaminergic systems are thought to play important roles in the motivational effects of ethanol. In the present experiments, we examined the effects of U99194A, a putative dopamine D(3) receptor antagonist, on ethanol-induced conditioned place preference, locomotor stimulation, taste aversion, and self-administration. In two separate studies with the use of a place conditioning procedure, adult male Swiss-Webster mice received six pairings of a tactile stimulus with ethanol (1 or 3 g/kg, i.p.), U99194A (20 mg/kg, i.p.), or ethanol + U99194A. For determination of ethanol-stimulated activity, subjects received U99194A at a dose of 0, 10, 20, or 30 mg/kg 15 min before ethanol at 0, 1, or 2 g/kg immediately before a 30-min locomotor activity test. In a taste conditioning procedure, subjects received five 1-h access periods to 0.2 M NaCl. After the first four access periods, subjects received ethanol at 0, 2, or 4 g/kg and U99194A at 0, 10, or 20 mg/kg. In an oral self-administration procedure, male C57BL/6J mice received U99194A at 0, 10, or 20 mg/kg, followed by 30-min access to 10% (wt./vol.) sucrose or 10% (vol./vol.) ethanol in 10% sucrose. The acquisition of ethanol-induced conditioned place preference was enhanced by U99194A. However, U99194A did not produce significant preference alone. U99194A did not alter locomotor stimulation produced by an injection of ethanol at 2 g/kg. U99194A also did not alter the acquisition of ethanol-induced conditioned taste aversion and did not change oral ethanol self-administration. These results support the suggestion that dopamine D(3) receptors have specific involvement in ethanol reward, as measured by place conditioning, but are not important for ethanol-stimulated activity, ethanol taste aversion, or ethanol intake.
authors.affiliation: Department of Behavioral Neuroscience, L470, Portland Alcohol Research Center, Oregon Health & Science University, Portland, OR 97201-3098, USA. boycej@ohsu.edu
authors.forename: Janel M
authors.initials: JM
authors.lastname: Boyce
authors.forename: Fred O
authors.initials: FO
authors.lastname: Risinger
mesh_terms: D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D018492:Dopamine Antagonists / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D007189:Indans / Q000494:pharmacology; D008297:Male; D051379:Mice; D009042:Motivation; D009043:Motor Activity; D050637:Receptors, Dopamine D3
chemical_list: D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; C493594:Drd3 protein, mouse; D007189:Indans; D050637:Receptors, Dopamine D3; C086335:(5,6-dimethoxyindan-2-yl)dipropylamine; D000431:Ethanol