Assessment of the mixed discriminative stimulus effects of ethanol in a three-choice ethanol-dizocilpine-water discrimination in rats

G. J. Gatto, C. A. Bowen, Kathleen (Kathy) Grant

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Abstract

Previous drug discrimination studies have elucidated the importance of the NMDA, GABA(A) and 5-HT1 receptor systems in mediating the discriminative stimulus effects of ethanol. The present study used a three-choice drug discrimination paradigm in an attempt to determine whether the salient NMDA antagonistic effects were separable from other stimulus effects of ethanol. Adult Long-Evans rats (n = 7) were trained to discriminate ethanol (1.5 g/kg, intragastric (i.g.)), the uncompetitive NMDA antagonist dizocilpine (0.17 mg/kg, i.g.) or water (3.5 ml, i.g.) under a food-reinforced fixed-ratio 15 (FR15) schedule of reinforcement. Following training, substitution tests were conducted wth the GABA(A)/benzodiazepine (GABA(A)/BDZ) positive modulator pentobarbital (PB, 5.6-17 mg/kg, i.g.), the uncompetitive NMDA antagonist phencyclidine (PCP, 0.1-5.6 mg/kg, i.p.) and the 5-HT1 agonist RU 24969 (0.1-3.0 mg/kg, i.p.). Complete substitution of PCP (ED50, 0.9 mg/kg) for dizocilpine was found in all animals. Conversely, PB (ED50, 10 mg/kg) substituted fully for ethanol in five of seven animals, whereas RU 24969 (ED50, 1.4 mg/kg) completely substituted for ethanol in only three of seven animals tested. The results demonstrate that a three-choice discrimination using dizocilpine, ethanol and water as training conditions can be established in rats. By contrasting the discriminative stimulus effects of an uncompetitive NMDA antagonist to ethanol, the ethanol-like effects of pentobarbital and RU 24969 are attenuated compared to previous studies of two-choice ethanol water discrimination.

Original languageEnglish (US)
Pages (from-to)601-613
Number of pages13
JournalBehavioural Pharmacology
Volume6
Issue number5-6
Publication statusPublished - 1995
Externally publishedYes

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Keywords

  • dizocilpine
  • ethanol
  • NMDA
  • pentobarbital
  • rat
  • RU 24969
  • three-choice drug discrimination

ASJC Scopus subject areas

  • Neuroscience(all)
  • Pharmacology

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