Chronic nicotine causes functional upregulation of ionotropic glutamate receptors mediating hippocampal noradrenaline and striatal dopamine release.
It has been proposed that (-)-nicotine can activate release-stimulating presynaptic nicotinic acetylcholine receptors (nAChRs) on glutamatergic nerve terminals to release glutamate, which in turn stimulates the release of noradrenaline (NA) and dopamine (DA) via presynaptic ionotropic glutamate receptors on catecholaminergic terminals. The objective of this study was to compare the function of N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methylisoxazide-4-propionic acid (AMPA) glutamate receptors in synaptosomes of rat hippocampus and striatum following acute and chronic (-)-nicotine administration. In hippocampal synaptosomes, prelabeled with [3H]NA, both the NMDA- and AMPA-evoked releases were higher in (-)-nicotine-treated (10 days) than in (-)-nicotine-treated (1 day) or vehicle-treated (1 or 10 days) rats. In striatal synaptosomes prelabeled with [3H]DA, the NMDA-evoked, but not the AMPA-evoked, release of [3H]DA was higher in (-)-nicotine-treated (10 days) than in nicotine-treated (1 day) or vehicle-treated (1 or 10 days) animals. Chronic (-)-nicotine did not affect catecholamine uptake, basal release and release evoked by high-K+ depolarization. Thus, chronic exposure to nicotine enhances the function of ionotropic glutamate receptors mediating noradrenaline release in the hippocampus and dopamine release in the striatum.
Risso
Francesca
F
Sezione di Farmacologia e Tossicologia, Dipartimento di Medicina Sperimentale, Università Degli Studi di Genova, Viale Cembrano 4, Genoa 16148, Italy.
Parodi
Monica
M
Grilli
Massimo
M
Molfino
Francesca
F
Raiteri
Maurizio
M
Marchi
Mario
M
D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000187:drug effects; D017470:Receptors, Glutamate / Q000096:biosynthesis*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D018690:Excitatory Amino Acid Agonists; D018722:Nicotinic Agonists; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D009538:Nicotine; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D011188:Potassium; D004298:Dopamine; D009638:Norepinephrine