Mechanisms of nicotine actions on dorsal raphe serotoninergic neurons.
Nicotine, locally administered into the dorsal raphe nucleus (DRN) of rat midbrain slices, increased the discharge rate of 70% of serotoninergic neurons, decreased it in 30% and induced reciprocal oscillatory increases in serotonin (5-hydroxytryptamine, 5-HT) and gamma-aminobutyric acid (GABA) release. All of nicotine's stimulatory effects were maximal at 2.15 microM. Bicuculline, a GABA(A) receptor antagonist, increased the firing rate in 64% of serotoninergic neurons, decreased it in 36% and augmented serotonin and GABA release. Bicuculline increased nicotine's stimulatory effects on firing rate but did not reverse the inhibitory ones. N-[2-[4-(2-Methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinil-cyclohexanecarboxamide (WAY-100635), a 5-HT(1A) receptor antagonist, increased the firing rate of 88% of serotoninergic neurons, as well as serotonin and GABA release and reversed nicotine's inhibitory action on serotoninergic neurons. These data suggest that nicotine decreases the firing rate of one third of serotoninergic neurons through serotonin release and increases the firing rate of the remaining two thirds, due to stronger stimulatory than indirect inhibitory effects.
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004594:Electrophysiology; D018756:GABA Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008636:Mesencephalon / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011903:Raphe Nuclei / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018756:GABA Antagonists; D018722:Nicotinic Agonists; D010879:Piperazines; D011725:Pyridines; D012702:Serotonin Antagonists; D012701:Serotonin; D005680:gamma-Aminobutyric Acid; D009538:Nicotine; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D001640:Bicuculline