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 γ-aminobutyric acid (GABA) release....

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Bibliographic Details
Published in:European journal of pharmacology 2002-09, Vol.452 (1), p.77-82
Main Authors: Mihailescu, Stefan, Guzmán-Marı́n, Rubén, del Carmen Frı́as Domı́nguez, Marı́a, Drucker-Colı́n, René
Format: Article
Language:English
Subjects:
5-HT (5-Hydroxytryptamine)
Animals
Bicuculline - pharmacology
Biological and medical sciences
Chromatography, High Pressure Liquid
Dorsal raphe nucleus
Electrophysiology
GABA (γ-Aminobutyric acid)
GABA Antagonists - pharmacology
gamma-Aminobutyric Acid - metabolism
In Vitro Techniques
Male
Medical sciences
Mesencephalon - cytology
Mesencephalon - drug effects
Mesencephalon - physiology
Neurons - drug effects
Neurons - metabolism
Neuropharmacology
Neurotransmitters. Neurotransmission. Receptors
Nicotine
Nicotine - pharmacology
Nicotinic Agonists - pharmacology
Patch-Clamp Techniques
Pharmacology. Drug treatments
Piperazines - pharmacology
Pyridines - pharmacology
Raphe Nuclei - cytology
Raphe Nuclei - drug effects
Raphe Nuclei - metabolism
Rats
Rats, Wistar
serotonin
Serotonin - metabolism
Serotonin - physiology
Serotonin Antagonists - pharmacology
Serotoninergic system
Tobacco, tobacco smoking
Toxicology
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Summary: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 γ-aminobutyric acid (GABA) release. All of nicotine's stimulatory effects were maximal at 2.15 μM. 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.
ISSN:0014-2999
1879-0712
DOI:10.1016/S0014-2999(02)02244-6