Presynaptic inhibition of glutamate transmission by α2 receptors in the VTA

Autor:	María E. Vélez-Hernández, Johnny D. Figueroa, Francisco Arencibia-Albite, David Alexander Schwarz, Rafael Vázquez-Torres, María C. Velásquez-Martinez, Carlos A. Jiménez-Rivera
Rok vydání:	2012
Předmět:	Postsynaptic Current General Neuroscience Dopaminergic Glutamate receptor Biology Neurotransmission Pharmacology Inhibitory postsynaptic potential Ventral tegmental area medicine.anatomical_structure Dopamine medicine Excitatory postsynaptic potential Neuroscience medicine.drug
Zdroj:	European Journal of Neuroscience. 35:1406-1415
ISSN:	0953-816X
Popis:	The ventral tegmental area (VTA) forms part of the mesocorticolimbic system and plays a pivotal role in reward and reinforcing actions of drugs of abuse. Glutamate transmission within the VTA controls important aspects of goal-directed behavior and motivation. Noradrenergic receptors also present in the VTA have important functions in the modulation of neuronal activity. Here we studied the effects of alpha-2 noradrenergic receptor activation in the alteration of glutamate neurotransmission in VTA dopaminergic neurons from male Sprague-Dawley rats. We used whole cell patch clamp recordings from putative VTA dopaminergic neurons and measured excitatory postsynaptic currents. Clonidine (40 μM) and UK 13,408 (40 μM), both alpha-2 receptor agonists, reduced (~ 40%) the amplitude of glutamate-induced excitatory postsynaptic currents. After clonidine administration, there was a dose-dependent reduction over the concentration range of 15–40 μM. Using yohimbine (20μM) and two other alpha-2 adrenergic receptor antagonists, idaxozan (40 μM) and atipemazole (20μM), we demonstrated that the inhibitory action is specifically mediated by alpha-2 receptors. Moreover, by inhibiting protein kinases with H-7 (75 μM), Rp-adenosine 3′,5′-cyclic (11 μM) and chelerythrine (1 μM) it was shown that the clonidine-induced inhibition seems to involve a selective activation of the protein kinase C intracellular pathway. An increased paired-pulse ratios and changes in spontaneous and miniature excitatory postsynaptic currents frequencies but not amplitudes indicated that the alpha-2 agonist’s effect was presynaptically mediated. It is suggested that the suppression of glutamate excitatory inputs onto VTA dopaminergic neurons might be relevant in the regulation of reward and drug seeking behaviors.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::100a1fbbeb7ea629c31b688d821fbe94 https://doi.org/10.1111/j.1460-9568.2012.08029.x Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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