Attenuation of the discriminative stimulus effects of ethanol by the benzodiazepine partial inverse agonist Ro 15-4513

Behav Pharmacol. 1997 Jun;8(2-3):139-46.

Abstract

The aim of the present study was to investigate whether ethanol training affects the ability of Ro 15-4513 to block the discriminative stimulus effects of ethanol dose differentially. Three different groups of rats were trained to discriminate 1.0 g/kg ethanol (n = 8), 1.5 g/kg ethanol (n = 7) or 2.0 g/kg ethanol (n = 8) from water in a two-lever, food-reinforced procedure. Ethanol and water were administered by gavage 20 min before the onset of the session. When the discrimination performance was stable, rats were pretreated with Ro 15-4513 (1-17 mg/kg; i.p.) 5 min before the administration of ethanol. Ro 15-4513 attenuated the discriminative stimulus effects of 1.0 and 1.5 g/kg ethanol but not 2.0 g/kg ethanol in each of the ethanol training groups. Overall, blockade of the discriminative stimulus effects of 1.0 and 1.5 g/kg ethanol by 5.6 mg/kg Ro 15-4513 occurred without significantly altering response rates or blood ethanol concentrations. A decrease in blood ethanol concentration was, however, found with 17 mg/kg Ro 15-4513 in combination with 2.0 g/kg ethanol. These results suggest that the benzodiazepine partial inverse agonist, Ro 15-4513, can attenuate the discriminative stimulus effects associated with low to moderate doses of ethanol (1.0-1.5 g/kg).

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Azides / pharmacology*
  • Benzodiazepines / pharmacology*
  • Central Nervous System Depressants / blood
  • Central Nervous System Depressants / pharmacology*
  • Discrimination Learning / drug effects
  • Discrimination, Psychological / drug effects*
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Ethanol / blood
  • Ethanol / pharmacology*
  • Male
  • Rats

Substances

  • Azides
  • Central Nervous System Depressants
  • Benzodiazepines
  • Ethanol
  • Ro 15-4513