Presynaptic α4β2 nicotinic acetylcholine receptors increase glutamate release and serotonin neuron excitability in the dorsal raphe nucleus

Several behavioral effects of nicotine are mediated by changes in serotonin (5-HT) release in brain areas that receive serotonergic afferents from the dorsal raphe nucleus (DRN). In vitro experiments have demonstrated that nicotine increases the firing activity in the majority of DRN 5-HT neurons an...

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Vydáno v:The Journal of neuroscience Ročník 32; číslo 43; s. 15148
Hlavní autoři: Garduño, Julieta, Galindo-Charles, Luis, Jiménez-Rodríguez, Javier, Galarraga, Elvira, Tapia, Dagoberto, Mihailescu, Stefan, Hernandez-Lopez, Salvador
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States 24.10.2012
Témata:
6-Cyano-7-nitroquinoxaline-2,3-dione - pharmacology
Acetylcholine - pharmacology
Aconitine - analogs & derivatives
Aconitine - pharmacology
Animals
Animals, Newborn
Atropine - pharmacology
Bicuculline - pharmacology
Cadmium Chloride - pharmacology
Chelating Agents - pharmacology
Cholinergic Agonists - pharmacology
Dihydro-beta-Erythroidine - pharmacology
Egtazic Acid - analogs & derivatives
Egtazic Acid - pharmacology
Electric Stimulation
Enzyme Inhibitors - pharmacology
Excitatory Amino Acid Antagonists - pharmacology
Excitatory Postsynaptic Potentials - drug effects
Excitatory Postsynaptic Potentials - physiology
GABA Antagonists - pharmacology
Glutamic Acid - physiology
In Vitro Techniques
Indoles - pharmacology
Male
Muscarinic Antagonists - pharmacology
Nicotine - analogs & derivatives
Nicotine - pharmacology
Nicotinic Antagonists - pharmacology
Patch-Clamp Techniques
Physostigmine - pharmacology
Presynaptic Terminals - drug effects
Presynaptic Terminals - physiology
Raphe Nuclei - cytology
Rats
Rats, Wistar
Receptors, Nicotinic - physiology
Ryanodine - pharmacology
Serotonergic Neurons - cytology
Serotonergic Neurons - physiology
Serotonin - metabolism
Sodium Channel Blockers - pharmacology
Tetrodotoxin - pharmacology
ISSN:1529-2401, 1529-2401
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Popis
Shrnutí:Several behavioral effects of nicotine are mediated by changes in serotonin (5-HT) release in brain areas that receive serotonergic afferents from the dorsal raphe nucleus (DRN). In vitro experiments have demonstrated that nicotine increases the firing activity in the majority of DRN 5-HT neurons and that DRN contains nicotinic acetylcholine receptors (nAChRs) located at both somata and presynaptic elements. One of the most common presynaptic effects of nicotine is to increase glutamate release. Although DRN receives profuse glutamatergic afferents, the effect of nicotine on glutamate release in the DRN has not been studied in detail. Using whole-cell recording techniques, we investigated the effects of nicotine on the glutamatergic input to 5-HT DRN neurons in rat midbrain slices. Low nicotine concentrations, in the presence of bicuculline and tetrodotoxin (TTX), increased the frequency but did not change the amplitude of glutamate-induced EPSCs, recorded from identified 5-HT neurons. Nicotine-induced increase of glutamatergic EPSC frequency persisted 10-20 min after drug withdrawal. This nicotinic effect was mimicked by exogenous administration of acetylcholine (ACh) or inhibition of ACh metabolism. In addition, the nicotine-induced increase in EPSC frequency was abolished by blockade of α4β2 nAChRs, voltage-gated calcium channels, or intracellular calcium signaling but not by α7 nAChR antagonists. These data suggest that both nicotine and endogenous ACh can increase glutamate release through activation of presynaptic α4β2 but not α7 nAChRs in the DRN. The effect involves long-term changes in synaptic function, and it is dependent on voltage-gated calcium channels and presynaptic calcium stores.
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1529-2401
1529-2401
DOI:10.1523/JNEUROSCI.0941-12.2012