The competitive N-methyl-D-aspartate (NMDA) antagonist CGS 19755 attenuates the rate-decreasing effects of NMDA in rhesus monkeys without producing ketamine-like discriminative stimulus effects

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Abstract

The purported competitive excitatory amino acid antagonist CGS 19755 was compared to the non-competitive antagonists ketamine and MK-801 in three rhesus monkeys discriminating between 1.78 mg/kg of ketamine and saline while responding under a fixed-ratio 100 schedule of food presentation. MK-801 substituted completely for the ketamine discriminative stimulus and was 32 times more potent than ketamine as a discriminative stimulus. CGS 19755 was studies using sinlge and cumulative dosing procedures up to a dose of 10.0 mg/kg; for all conditions, CGS 19755 produced responding exclusively on the saline lever and had only modest rate-decreasing effects. N-Methyl-D-aspartate administered alone also did not produce ketamine-appropriate responding but did decrease response rates in a dose-related manner. N-Methyl-D-aspartate eliminated responding in all monkeys at doses of 5.6-10.0 mg/kg. MK-801 and ketamine antagonized the rate-decreasing effects of N-methyl-D-asparate, however, ketamine was most effective as an antagonist at doses that decreased response effects of N-methyl-D-asparate, however, ketamine was most the rate-decreasing effects of N-methyl-D-aspartate and shifted the N-methyl-D-aspartate dose-effect curve more than 5-fold to the right. The magnitude of antagonism of N-methyl-D-aspartate appeared to be somewhat greater with CGS 19755 than with MK-801 or ketamine. Thus, a competitive (CGS 19755) and some non-competitive (MK-801 and ketamine) excitatory amino acid antagonists can attenuate the rate-decreasing effects of N-methyl-D-aspartate. Surprisingly, the results suggest that antagonism of N-methyl-D-aspartate is not sufficient to produce ketamine-like discriminative stimulus effects under these conditions in rhesus monkeys.

Original languageEnglish (US)
Pages (from-to)133-139
Number of pages7
JournalEuropean Journal of Pharmacology
Volume159
Issue number2
DOIs
StatePublished - Jan 10 1989
Externally publishedYes

Keywords

  • (Rhesus monkey)
  • CGS 19755 (1-(cis-2-carboxypiperidine-4-yl)-methyl-1-phosphonic acid)
  • Drug discrimination
  • MK-801
  • NMDA (N-methyl-D-aspartate)
  • Schedule-controlled responding

ASJC Scopus subject areas

  • Pharmacology

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