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

Daily repeated administration of cocaine (15 mg/kg, over a 7-day period) developed reverse tolerance to the ambulation-accelerating effect of cocaine. Intraperitoneal administration of ginseng total saponin (GTS, 100 and 200 mg/kg of body weight) prior to and during chronic administration of cocaine inhibited the development of reverse tolerance. Dopamine receptor supersensitivity was also developed in reverse tolerant mice that had received the same cocaine. The development of dopamine receptor supersensitivity was evidenced by the enhanced hypothermic response to apomorphine (1 mg/kg) and the enhanced ambulatory activity of apomorphine (4 mg/kg). GTS also prevented the development of dopamine receptor supersensitivity induced by the chronic administration of cocaine. These results provide that GTS may be useful for the prevention and therapy of the adverse action of cocaine. It is concluded that the development of reverse tolerance to the ambulation-accelerating effect of cocaine may be associated with the enhanced dopamine receptor sensitivity because both phenomena were blocked by GTS.