Nicotine inhibits firing activity of dorsal raphe 5-HT neurones in vivo.
It is established that the brain monoaminergic systems are among the main targets of several dependence-inducing drugs, including nicotine. In the present study extracellular electrophysiological recordings were performed to investigate the effects of nicotine on dorsal raphe 5-HT neurones. Nicotine, administered systemically (50-400 microg/kg, i.v.) in chloral hydrate-anaesthetised rats, induced a transient inhibition of the majority of 5-HT neurones recorded (38 of 45). The inhibition was rapid in onset (about 30 s) and the firing rate returned to baseline within 1-3 min. No apparent tachyphylaxis was observed to this inhibitory effect. The centrally acting nicotine antagonist mecamylamine (4 mg/kg, i.v.), but not the peripherally acting nicotine antagonist chlorisondamine (0.3 mg/kg, i.v.) antagonised the nicotine-induced inhibition of 5-HT neurones. The inhibition of 5-HT neurones was also blocked with a selective 5-HT1A receptor antagonist (WAY 100635; 0.1 mg/kg, i.v.), indicating a possible involvement of somato-dendritic 5-HT1A receptors in the effect of nicotine. Interestingly, microiontophoretic application of nicotine into the dorsal raphe failed to inhibit 5-HT neurones, suggesting an indirect effect of nicotine on 5-HT neurones, possibly involving afferent pathways.
Karolinska Institute, Department of Physiology and Pharmacology, Stockholm, Sweden. goran.engberg@fyfa.ki.se
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Engberg
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Erhardt
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Sharp
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Hajós
D000818:Animals; D002714:Chlorisondamine / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D004594:Electrophysiology; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008839:Microelectrodes; D009474:Neurons / Q000187:drug effects*; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D010830:Physostigmine / Q000494:pharmacology; D011903:Raphe Nuclei / Q000166:cytology* / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*
D002800:Cholinesterase Inhibitors; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D012701:Serotonin; D009538:Nicotine; D010830:Physostigmine; D002714:Chlorisondamine