Nicotine inhibits firing activity of dorsal raphe 5-HT neurones in vivo

It is established that the brain monoaminergic systems are among the main t argets of several dependence-inducing drugs, including nicotine. In the pre sent study extracellular electrophysiological recordings were performed to investigate the effects of nicotine on dorsal raphe 5-HT neurones. Nicotine, administered systemically (50-400 mu g/kg, i.v.) in chloral hydra te-anaesthetised rats, induced a transient inhibition of the majority of 5- HT neurones recorded (38 of 45). The inhibition was rapid in onset (about 3 0 s) and the firing rate returned to baseline within 1-3 min. No apparent t achyphylaxis was observed to this inhibitory effect. The centrally acting n icotine antagonist mecamylamine (4 mg/kg, i.v.), but not the peripherally a cting nicotine antagonist chlorisondamine (0.3 mg/kg, i.v,) antagonised the nicotine-induced inhibition of 5-HT neurones. The inhibition of 5-HT neuro nes was also blocked with a selective 5-HT1A receptor antagonist (WAY 10063 5; 0.1 mg/kg, i.v.), indicating a possible involvement of somatodendritic 5 -HT1A receptors in the effect of nicotine. Interestingly, microiontophoreti c application of nicotine into the dorsal raphe failed to inhibit 5-HT neur ones, suggesting an indirect effect of nicotine on 5-HT neurones, possibly involving afferent pathways.