Nitric oxide synthase inhibitors block behavioral sensitization to methamphetamine in mice

European Journal of Pharmacology
M Ohno, S Watanabe

Abstract

Repeated administration of methamphetamine (1.0 mg/kg) once daily for 7 consecutive days resulted in an augmentation of the locomotor-activating effect of methamphetamine (0.5 mg/kg) challenged 72 h after the last injection. Administration of the nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine (10 and 30 mg/kg), before daily methamphetamine injections dose dependently prevented the development of behavioral sensitization to subsequent methamphetamine challenge. The mice given another NO synthase inhibitor, NG-nitro-L-arginine methyl ester (100 mg/kg), before daily methamphetamine injections showed significantly less locomotor activity in response to 0.5 mg/kg methamphetamine challenge than the mice given daily methamphetamine alone. Such effects were not observed when the inactive isomer, NG-nitro-D-arginine methyl ester (100 mg/kg), was administered daily prior to methamphetamine. Both NO synthase inhibitors exerted the acute effect to reduce spontaneous and methamphetamine-stimulated locomotor activity, while neither spontaneous locomotion nor hyperlocomotion in response to 1.0 mg/kg methamphetamine was altered 72 h after repeated administration of NG-nitro-L-arginine (30 mg/kg) or NG-nitro-L-arginine methyl ester (...Continue Reading

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