POSSIBLE EXPLANATIONS FOR THE ANTAGONISM BY NICOTINE AGAINST RESERPINE-INDUCED DEPLETION OF MONOAMINES IN MOUSE-BRAIN

The inhibitory effect of nicotine pretreatment on reserpine-induced de pletion of monoamines in mouse brain was investigated. The depletion o f brain monoamines by 24 h after intraperitoneal injection of reserpin e (2 mg/kg) was dose-dependently inhibited by nicotine (0.3-10 mg/kg, s.c.) pretreatment 20 min before reserpine injection. This effect of n icotine was more marked on dopamine depletion than on noradrenaline or 5-hydroxytryptamine depletion. The nicotine pretreatment also inhibit ed the reserpine-induced hypothermia and decrease in the locomotor act ivity. When reserpine (2 mg/kg) was injected intraperitoneally, the in hibitory effect of nicotine (3 mg/kg, s.c.) on the reserpine-induced d epletion of brain monoamines and heart noradrenaline was not antagoniz ed by hexamethonium (8 mg/kg, s.c.) but rather potentiated by mecamyla mine (2 mg/kg, s.c.). However, when reserpine (0.5 mg/kg) was injected intravenously, pretreatment with nicotine (3 mg/kg, s.c.) inhibited t he reserpine-induced dopamine depletion only, and this effect of nicot ine was completely blocked by mecamylamine but not by hexamethonium. T hese results suggest that inhibitory effect of nicotine on the intrape ritoneal reserpine-induced depletion of brain monoamines is due to an inhibition of absorption of reserpine, and that central nicotinic acti on is also involved in the antagonism by nicotine of reserpine-induced dopamine depletion.