THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS Copyright C issa by The American Society for Pharmacology and Experimental Therapeutics Behavioral Tolerance and Sensitization to CGS 19755, a Competitive N-Methyl-D-Aspartate Receptor Antagonist

Competitive N-methyl-D-aspartate (NMDA) receptor antagonists, including CGS 1 9755, have the ability to antagonize NMDA-induced convulsions, to cause ataxia and, at high doses, to increase spontaneous locomotor activity. It was of interest to determine whether or not repeated treatment with CGS 19755 would induce tolerance to some or all of these effects. CGS 1 9755 was administered to mice twice daily for 1 4 days at 54 mg/kg i.p. per injection. One day after the last repeated injection, mice were challenged with vehicle or one of several doses of CGS 19755 (1 0, 30, 54 and 1 00 mg/kg) and were tested for evidence of motor impairment (using righting reflex and traction tests), for spontaneous locomotor activity and for the threshold dose of NMDA required to induce convulsions. When challenged with CGS 1 9755, mice that had previously received only vehicl