Please use this identifier to cite or link to this item:
|Title:||Prolonged nicotine exposure down-regulates presynaptic NMDA receptors in dopaminergic terminals of the rat nucleus accumbens||Authors:||Salamone, Alessia
Tomé, Angelo R.
Cunha, Rodrigo A.
|Keywords:||Nicotinic receptors; NMDA receptors; Calcium levels; Neurotransmitter release; Isolated nerve endings; Nucleus accumbens||Issue Date:||Apr-2014||Publisher:||Elsevier||Citation:||SALAMONE, Alessia [et al.] - Prolonged nicotine exposure down-regulates presynaptic NMDA receptors in dopaminergic terminals of the rat nucleus accumbens. "Neuropharmacology". ISSN 0028-3908. Vol. 79 (2014) p. 488-497||Serial title, monograph or event:||Neuropharmacology||Volume:||79||Abstract:||The presynaptic control of dopamine release in the nucleus accumbens (NAc) by glutamate and acetylcholine has a profound impact on reward signaling. Here we provide immunocytochemical and neurochemical evidence supporting the co-localization and functional interaction between nicotinic acetylcholine receptors (nAChRs) and N-methyl-D-aspartic acid (NMDA) receptors in dopaminergic terminals of the NAc. Most NAc dopaminergic terminals possessed the nAChR α4 subunit and the pre-exposure of synaptosomes to nicotine (30 μM) or to the α4β2-containing nAChR agonist 5IA85380 (10 nM) selectively inhibited the NMDA (100 μM)-evoked, but not the 4-aminopyridine (10 μM)-evoked, [3H] dopamine outflow; this inhibition was blunted by mecamylamine (10 μM). Nicotine and 5IA85380 pretreatment also inhibited the NMDA (100 μM)-evoked increase of calcium levels in single nerve terminals, an effect prevented by dihydro-β-erythroidine (1 μM). This supports a functional interaction between α4β2-containing nAChR and NMDA receptors within the same terminal, as supported by the immunocytochemical co-localization of α4 and GluN1 subunits in individual NAc dopaminergic terminals. The NMDA-evoked [3H]dopamine outflow was blocked by MK801 (1 μM) and inhibited by the selective GluN2B-selective antagonists ifenprodil (1 μM) and RO 25-6981 (1 μM), but not by the GluN2A-preferring antagonists CPP-19755 (1 μM) and ZnCl2 (1 nM). Notably, nicotine pretreatment significantly decreased the density of biotin-tagged GluN2B proteins in NAc synaptosomes. These results show that nAChRs dynamically and negatively regulate NMDA receptors in NAc dopaminergic terminals through the internalization of GluN2B receptors.||URI:||http://hdl.handle.net/10316/27138||ISSN:||0028-3908||DOI:||10.1016/j.neuropharm.2013.12.014||Rights:||openAccess|
|Appears in Collections:||I&D CNC - Artigos em Revistas Internacionais|
FMUC Medicina - Artigos em Revistas Internacionais
FCTUC Ciências da Vida - Artigos em Revistas Internacionais
Show full item record
Files in This Item:
|Prolonged nicotine exposure down-regulates presynaptic NMDA receptors.pdf||573.23 kB||Adobe PDF||View/Open|
checked on Nov 8, 2019
WEB OF SCIENCETM
checked on Jun 25, 2019
Page view(s) 50367
checked on Dec 10, 2019
checked on Dec 10, 2019
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.