Iptakalim inhibits nicotine-induced enhancement of extracellular dopamine and glutamate levels in the nucleus accumbens of rats.

Iptakalim (Ipt) is a novel ATP-sensitive potassium channel opener. It has been reported that Ipt inhibited cocaine-induced dopamine and glutamate release, suggesting that Ipt may regulate drug addiction. Recently, we found that Ipt blocked nicotinic acetylcholine receptor (nAChR)-mediated currents in a heterologously expressed SH-EP1 cell line and in native midbrain dopamine neurons. In the present study, we examined whether Ipt prevents nicotine-induced neurotransmitter release in the nucleus accumbens (NAc) using in vivo microdialysis methods in awake, freely moving rats. Ipt was administered through a microdialysis probe, following systemic administration of nicotine (0.5 mg/kg, s.c.). The results show that acute nicotine treatment induced an increase of both dopamine and glutamate levels in the rat NAc, and that Ipt significantly attenuated nicotine's effects in a concentration-dependent manner. Therefore, Ipt may serve as a novel compound to block nicotine-induced dopamine and glutamate release in the brain reward center, in turn decreasing nicotine reinforcement and dependence.