BLOCKADE BY GINSENG TOTAL SAPONIN OF THE DEVELOPMENT OF METHAMPHETAMINE REVERSE TOLERANCE AND DOPAMINE-RECEPTOR SUPERSENSITIVITY IN MICE

Repeated administration of methamphetamine (2 mg/kg) developed reverse tolerance to the ambulation-accelerating effect. Intraperitoneal admi nistration of ginseng total saponin (GTS, 200 mg/kg of body weight) pr ior to and during chronic administration of methamphetamine inhibited the development of reverse tolerance. Dopamine receptor supersensitivi ty was also developed in reverse tolerant mice which had received the same methamphetamine. The development of dopamine receptor supersensit ivity was evidenced by the enhanced hypothermic response to apomorphin e (1 mg/kg) and the enhanced ambulatory activity of apomorphine (4 mg/ kg). GTS also prevented the development of dopamine receptor supersens itivity induced by the chronic administration of methamphetamine. Thes e results show that GTS may be useful for the prevention of and therap y for the adverse action of methamphetamine. It is concluded that the development of reverse tolerance to methamphetamine may be associated with the enhanced dopamine receptor supersensitivity since both phenom ena were blocked by GTS.