Nicotine increases GABAergic input on rat dorsal raphe serotonergic neurons through alpha7 nicotinic acetylcholine receptor.
J Neurophysiol
; 112(12): 3154-63, 2014 Dec 15.
Article
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| MEDLINE
| ID: mdl-25231613
ABSTRACT
The dorsal raphe nucleus (DRN) contains large populations of serotonergic (5-HT) neurons. This nucleus receives GABAergic inhibitory afferents from many brain areas and from DRN interneurons. Both GABAergic and 5-HT DRN neurons express functional nicotinic acetylcholine receptors (nAChRs). Previous studies have demonstrated that nicotine increases 5-HT release and 5-HT DRN neuron discharge rate by stimulating postsynaptic nAChRs and by increasing glutamate and norepinephrine release inside DRN. However, the influence of nicotine on the GABAergic input to 5-HT DRN neurons was poorly investigated. Therefore, the aim of this work was to determine the effect of nicotine on GABAergic spontaneous inhibitory postsynaptic currents (sIPSCs) of 5-HT DRN neurons and the subtype of nAChR(s) involved in this response. Experiments were performed in coronal slices obtained from young Wistar rats. GABAergic sIPSCs were recorded from post hoc-identified 5-HT DRN neurons with the whole cell voltage patch-clamp technique. Administration of nicotine (1 µM) increased sIPSC frequency in 72% of identified 5-HT DRN neurons. This effect was not reproduced by the α4ß2 nAChR agonist RJR-2403 and was not influenced by TTX (1 µM). It was mimicked by the selective agonist for α7 nAChR, PNU-282987, and exacerbated by the positive allosteric modulator of the same receptor, PNU-120596. The nicotine-induced increase in sIPSC frequency was independent on voltage-gated calcium channels and dependent on Ca(2+)-induced Ca(2+) release (CICR). These results demonstrate that nicotine increases the GABAergic input to most 5-HT DRN neurons, by activating α7 nAChRs and producing CICR in DRN GABAergic terminals.
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Base de datos:
MEDLINE
Asunto principal:
Agonistas Nicotínicos
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Potenciales Postsinápticos Inhibidores
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Neuronas Serotoninérgicas
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Receptor Nicotínico de Acetilcolina alfa 7
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Núcleo Dorsal del Rafe
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Ácido gamma-Aminobutírico
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Nicotina
Límite:
Animals
Idioma:
En
Revista:
J Neurophysiol
Año:
2014
Tipo del documento:
Article
País de afiliación:
México