Effects of a range of dopamine receptor agonists and antagonists on ethanol intake in the rat.
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 D1 receptor partial agonist, SFK 38393 ((+/-)-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol hydrochloride), in a dose-dependent manner. The dopamine D2/D3 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 D1 receptor antagonist SCH 23390 (R-(+)-7-chloro-2,3,4,5-tetrahydro-3-methyl-1-phenyl-1H-3-benzazepine-8- ol), dopamine D2/D3 receptor antagonist raclopride and 5-HT2/D2 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 D1 and D2/D3 receptors playing opposing roles. Blockade of dopamine D2 receptors had no selective effect on ethanol consumption and ethanol preference.
Silvestre
J S
JS
Department of Pharmacology, Research Centre, Laboratorios Almirall, Barcelona, Spain.
O'Neill
M F
MF
Fernandez
A G
AG
Palacios
J M
JM
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000428:Alcohol Drinking / Q000523:psychology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D008297:Male; D020891:Raclopride; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000502:physiology; D050637:Receptors, Dopamine D3; D012457:Salicylamides / Q000494:pharmacology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D001552:Benzazepines; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; C493595:Drd3 protein, rat; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D012457:Salicylamides; D013764:Tetrahydronaphthalenes; D020891:Raclopride; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; C031349:7-hydroxy-2-N,N-dipropylaminotetralin