Modulation of Kappa-opioidergic Systems on Mecamylamine-precipitated Nicotine-withdrawal Aversion in Rats

The present study was designed to examine the modulation of the kappa-opioidergic system on mecamylamine-precipitated nicotine-withdrawal aversion. The nicotinic receptor antagonist mecamylamine, which is known to pass the blood-brain barrier, produced a place aversion in rats chronically treated with nicotine using an osmotic mini-pump. This effect was significantly attenuated by pretreatment with -opioid receptor agonists U50,488H (1.0 mg/kg, s.c.) and TRK-820 (0.03 mg/kg, s.c.). The attenuation of mecamylamine-precipitated nicotine-withdrawal aversion by U50,488H was completely reversed by the combination with a selective -opioid receptor antagonist nor-binaltorphimine (10.0 mg/kg, i.p.). These results suggest that the activation of endogenous -opioidergic systems can suppress the mecamylamine-precipitated nicotine-withdrawal aversion.