N-methyl-d-aspartate receptor antagonism in the ventral tegmental area diminishes the systemic nicotine-induced dopamine release in the nucleus accumbens

摘要: Abstract Systemic nicotine enhances burst firing of dopamine neurons in the ventral tegmental area and release nucleus accumbens, mainly via stimulation nicotinic acetylcholine receptors area. Given that both neuronal activity mesolimbic terminal are regulated by excitatory amino acid inputs to facilitates glutamatergic transmission brain, we investigated putative role ionotropic glutamate within for effects on accumbens using microdialysis, with one probe implanted drug application another ipsilateral measuring dopamine, awake rats. (0.5 mg/kg, s.c.) infusion (1.0 mM) into increased output accumbens. Intrategmental α -amino-3-hydroxy-5-methylisoxazole-4-propionate (0.1 mM) or N -methyl- d -aspartate (0.3 mM) accumbal release; these were antagonized concomitant a selective antagonist at receptors, 2-amino-5-phosphonopentanoic (0.3 mM), non- 6-cyano-7-nitroquinoxaline-2,3-dione respectively. Infusion either (0.3 1.0 mM) did not affect basal levels, whereas acid, but 6-cyano-7-nitroquinoxaline-2,3-dione, starting 40 min before injection dose-dependently attenuated nicotine-induced increase release. Concurrent intrategmental decreased These results indicate stimulatory action system is considerable extent mediated