期刊
NEUROPHARMACOLOGY
卷 63, 期 5, 页码 916-926出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2012.06.049
关键词
Nicotinic receptors; AMPA receptors; Nicotine treatment; Neurotransmitter release; Isolated nerve endings; Nucleus accumbens
资金
- Italian MIUR (Ministero dell'Istruzi'one, dell'Universita' e della Ricerca) from Compagnia di San Paolo, Turin, Italy [2009P7WHNR_003 AP, 2009R7WCZS_003 MM]
- University of Genoa 'Progetto Ricerca Ateneo'
- ALCOTRA [231]
- European Community [B51H10000000006]
Here we provide functional and immunocytochemical evidence supporting the presence on Nucleus Accumbens (NAc) dopaminergic terminals of cyclothiazide-sensitive, alfa-amino-3-hydroxy-5-methyl-4-isoxazolone propionate (AMPA) receptors, which activation causes Ca2+-dependent [H-3]dopamine ([H-3] DA) exocytosis. These AMPA receptors cross-talk with co-localized nicotinic receptors (nAChRs), as suggested by the finding that in vitro short-term pre-exposure of synaptosomes to 30 mu M nicotine caused a significant reduction of both the 30 mu M nicotine and the 100 mu M AMPA-evoked [H-3]DA overflow. Entrapping pep2-SVKI, a peptide known to compete for the binding of GluA2 subunit to scaffolding proteins involved in AMPA receptor endocytosis, in NAC synaptosomes prevented the nicotine-induced reduction of AMPA-mediated [H-3]DA exocytosis, while pep2-SVKE, used as negative control, was inefficacious. Immunocytochemical studies showed that a significant percentage of NAc terminals were dopaminergic and that most of these terminals also posses GluA2 receptor subunits. Western blot analysis of GluA2 immunoreactivity showed that presynaptic GluA2 proteins in NAc terminals were reduced in nicotine-pretreated synaptosomes when compared to the control. The nACh-AMPA receptor-receptor interaction was not limited to dopaminergic terminals since nicotine pre-exposure also affected the presynaptic AMPA receptors controlling hippocampal noradrenaline release, but not the presynaptic AMPA receptors controlling GABA and acetylcholine release. These observations could be relevant to the comprehension of the molecular mechanisms at the basis of nicotine rewarding. (C) 2012 Elsevier Ltd. All rights reserved.
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