R. Oishi et al., POSSIBLE EXPLANATIONS FOR THE ANTAGONISM BY NICOTINE AGAINST RESERPINE-INDUCED DEPLETION OF MONOAMINES IN MOUSE-BRAIN, Naunyn-Schmiedeberg's archives of pharmacology, 348(2), 1993, pp. 154-157
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.