Inhibition of Cocaine Sensitization by MK-801, a Noncompetitive N-Methyl-D-Aspartate (NMDA) Receptor Antagonist: Evaluation by Ambulatory Activity in Mice

The Japanese Journal of Pharmacology

Hisashi Kuribara²  Takayasu Asami¹  Iturou Ida³ 

[1] Gunma Prefectural Sawa Hospital of Psychiatry;Department of Neurobiology and Behavior, Behavior Research Institute, Gunma University School of Medicine;Department of Neuropsychiatry, Gunma University School of Medicine

关键词: MK-801;    Ambulatory activity;    Repeated administration;    Cocaine sensitization;    Drug interaction;   

DOI  :  10.1254/jjp.69.83

学科分类：药理学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(19)Cited-By(24)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.

【 授权许可】

Unknown