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

Eur J Pharmacol. 1996 Dec 30;318(2-3):257-65. doi: 10.1016/s0014-2999(96)00821-7.

Abstract

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.

MeSH terms

  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / pharmacology
  • Alcohol Drinking* / psychology
  • Animals
  • Benzazepines / pharmacology
  • Dopamine Agonists / pharmacology*
  • Dopamine Antagonists / pharmacology*
  • Male
  • Raclopride
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Dopamine D2 / physiology
  • Receptors, Dopamine D3
  • Salicylamides / pharmacology
  • Tetrahydronaphthalenes / pharmacology

Substances

  • Benzazepines
  • Dopamine Agonists
  • Dopamine Antagonists
  • Drd3 protein, rat
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • Salicylamides
  • Tetrahydronaphthalenes
  • Raclopride
  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
  • 7-hydroxy-2-N,N-dipropylaminotetralin