Jpn. J. Pharmacol. 69, 83-90 (1995)

Inhibition of cocaine sensitization by MK-801, a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist: Evaluation by ambulatory activity in mice

Iturou Ida (1), Takayasu Asami (2) and Hisashi Kuribara (3)

(1) Department of Neuropsychiatry, Gunma University School of Medicine, 3-39-22 Showa-machi, Maebashi 371, Japan
(2) Gunma Prefectural Sawa Hospital of Psychiatry, 2374 Ohaza-Kunisada, Azuma-mura, Sawa-gun, Gunma 379-22, Japan
(3) Department of Neurobiology and Behavior, Behavior Research Institute, Gunma University School of Medicine, 3-39-22 Showa-machi, Maebashi 371, Japan

Abstract: Alterations of cocaine effects, which were induced by prior repeated 5-time administration of MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine) (i.p.) alone or in combination with cocaine (s.c.) at 3- to 4-day intervals, were investigated by means of ambulatory activity in mice. The repeated administration of either cocaine (10 and 20 mg/kg) alone or MK-801 (0.3 mg/kg) alone progressively enhanced each drug's effect. The enhanced effects of cocaine and MK-801 were estimated to be 1.8-2.2 times and about 1.4 times, respectively, as great as those at the 1st administration. Although the coadministration of MK-801 with cocaine produced a significant enhancement in the ambulation-increasing effect, the comparatively higher doses of MK-801 (0.3 and 1 mg/kg) acted not only to reduce cocaine sensitivity but also to inhibit the development of cocaine sensitization. Thus, the mice that had been given MK-801 (0.3 and 1 mg/kg) alone 5 times showed lower sensitivities to cocaine (20 mg/kg) than the mice given saline alone. The mice coadministered MK-801 (0.3 and 1 mg/kg) with cocaine (10 and 20 mg/kg) also exhibited lower sensitivities to cocaine (10 and 20 mg/kg) than those given cocaine alone. However, MK-801 could not ameliorate the established sensitization to cocaine. Similar interactions have been demonstrated between MK-801 at 1 mg/kg, but not 0.3 mg/kg, and methamphetamine. The present results indicate that MK-801 can inhibit the development of sensitization to cocaine at a lower dose than that required to inhibit methamphetamine sensitization.

Keywords: MK-801, Ambulatory activity, Repeated administration, Cocaine sensitization, Drug interaction

Copyright© The Japanese Pharmacological Society 1995

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