title: Nicotinic α7 receptor activation selectively potentiates the function of NMDA receptors in glutamatergic terminals of the nucleus accumbens.
abstract: We here provide functional and immunocytochemical evidence supporting the co-localization and functional interaction between nicotinic acetylcholine receptors (nAChRs) and N-methyl-D-aspartic acid receptors (NMDARs) in glutamatergic terminals of the nucleus accumbens (NAc). Immunocytochemical studies showed that a significant percentage of NAc terminals were glutamatergic and possessed GluN1 and α7-containing nAChR. A short-term pre-exposure of synaptosomes to nicotine (30 µM) or choline (1 mM) caused a significant potentiation of the 100 µM NMDA-evoked [(3)H]D-aspartate ([(3)H]D-Asp) outflow, which was prevented by α-bungarotoxin (100 nM). The pre-exposure to nicotine (100 µM) or choline (1 mM) also enhanced the NMDA-induced cytosolic free calcium levels, as measured by FURA-2 fluorescence imaging in individual NAc terminals, an effect also prevented by α-bungarotoxin. Pre-exposure to the α4-nAChR agonists 5IA85380 (10 nM) or RJR2429 (1 µM) did not modify NMDA-evoked ([(3)H]D-Asp) outflow and calcium transients. The NMDA-evoked ([(3)H]D-Asp) overflow was partially antagonized by the NMDAR antagonists MK801, D-AP5, 5,7-DCKA and R(-)CPP and unaffected by the GluN2B-NMDAR antagonists Ro256981 and ifenprodil. Notably, pre-treatment with choline increased GluN2A biotin-tagged proteins. In conclusion, our results show that the GluN2A-NMDA receptor function can be positively regulated in NAc terminals in response to a brief incubation with α7 but not α4 nAChRs agonists. This might be a general feature in different brain areas since a similar nAChR-mediated bolstering of NMDA-induced ([(3)H]D-Asp) overflow was also observed in hippocampal synaptosomes.
authors.affiliation: Faculté de Médecine, Institut de Neurosciences des Systèmes Inserm UMR1106, Aix Marseille Université La Timone Marseille, France.
authors.forename: Stefania
authors.initials: S
authors.lastname: Zappettini
authors.affiliation: Department of Pharmacy, University of Genoa, Viale Cembrano Genoa, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Grilli
authors.affiliation: Department of Pharmacy, University of Genoa, Viale Cembrano Genoa, Italy.
authors.forename: Guendalina
authors.initials: G
authors.lastname: Olivero
authors.affiliation: Department of Pharmacy, University of Genoa, Viale Cembrano Genoa, Italy.
authors.forename: Jiayang
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Pharmacy, University of Genoa, Viale Cembrano Genoa, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Padolecchia
authors.affiliation: Department of Pharmacy, University of Genoa, Viale Cembrano Genoa, Italy ; Center of Excellence for Biomedical Research, University of Genoa Genoa, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Pittaluga
authors.affiliation: CNC-Center for Neuroscience and Cell Biology, University of Coimbra Coimbra, Portugal ; Department of Life Sciences, Faculty of Sciences and Technology, University of Coimbra Coimbra, Portugal.
authors.forename: Angelo R
authors.initials: AR
authors.lastname: Tomé
authors.affiliation: CNC-Center for Neuroscience and Cell Biology, University of Coimbra Coimbra, Portugal ; Faculty of Medicine, University of Coimbra Coimbra, Portugal.
authors.forename: Rodrigo A
authors.initials: RA
authors.lastname: Cunha
authors.affiliation: Department of Pharmacy, University of Genoa, Viale Cembrano Genoa, Italy ; Center of Excellence for Biomedical Research, University of Genoa Genoa, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Marchi
keywords: NMDA receptors; neurotransmitters release; nicotine treatment; nicotinic receptors; nucleus accumbens; synaptosomes