Nicotine and Stimulatory Effects on 5-HT DRN Neurons

Abstract A large number of behaviors and brain functions are modulated by nicotine through stimulation of presynaptic and, less frequently, postsynaptic nicotinic acetylcholine receptors (nAChRs). Clinical and experimental studies suggested that many of nicotine's behavioral effects are mediated by the brain serotonergic (5-HT) system. Dorsal raphe nucleus (DRN) neurons give most of the forebrain 5-HT innervation. Brain slice experiments indicated that nicotine increases the firing activity of 60–80% of 5-HT DRN neurons. The stimulatory effects of nicotine are direct, dependent on α7 and α4β2 somatodendritic nAChRs, and indirect, dependent on presynaptic nAChRs located on glutamatergic (α4β2 nAChRs) and noradrenergic (α7 nAChRs) terminals in the DRN. Microdialysis experiments indicated that systemic nicotine increases 5-HT release in a large number of cerebral areas. Likewise, it was shown that most of nicotine's behavioral effects are mediated by stimulation of various subtypes of 5-HT receptors.