Competitive NMDA receptor antagonist, CGP 40116, substitutes for the discriminative stimulus effects of ethanol

Eur J Pharmacol. 1996 Oct 31;314(3):277-80. doi: 10.1016/s0014-2999(96)00658-9.

Abstract

A drug discrimination procedure was used to compare the ability of competitive (CGP 37849, D,L-(E)-2-amino-4-methyl-5-phosphono-3-pentanoate; CGP 40116, D-(E)-2-amino-4-methyl-5-phosphono-3-pentanoate) and non-competitive (dizocilpine) NMDA receptor antagonists to substitute for ethanol in rats trained to discriminate between a 1.0 g/kg dose of ethanol (i.p.) and saline. Dizocilpine (0.1-0.3 mg/kg) substituted partially for ethanol at doses that markedly reduced the rate of responding. CGP 37849 (1.25-5.0 mg/kg) substituted partially for ethanol and suppressed the response rate. CGP 40116 (0.5-2.5 mg/kg), and active D-stereoisomer of CGP 37849, completely substituted (88%) for ethanol, and caused only moderate suppression of the response rate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Amino-5-phosphonovalerate / analogs & derivatives*
  • 2-Amino-5-phosphonovalerate / pharmacology
  • Animals
  • Binding, Competitive
  • Discrimination Learning / drug effects*
  • Dizocilpine Maleate / pharmacology
  • Dose-Response Relationship, Drug
  • Ethanol / pharmacology*
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Male
  • Rats
  • Rats, Wistar
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*
  • Stereoisomerism

Substances

  • Excitatory Amino Acid Antagonists
  • Receptors, N-Methyl-D-Aspartate
  • 2-amino-4-methyl-5-phosphono-3-pentenoic acid
  • Ethanol
  • Dizocilpine Maleate
  • 2-Amino-5-phosphonovalerate