Westerink, Ben H C and Enrico, Paolo and Feimann , J. and De Vries, Jan B. (1998) The pharmacology of mesocortical dopamine neurons: a dual-probe microdialysis study in the ventral tegmental area and prefrontal cortex of the rat brain. Journal of Pharmacology and Experimental Therapeutics, Vol. 285 (1), p. 143-154. eISSN 1521-0103. Article.
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Receptor-specific compounds were applied by retrograde microdialysis to the ventral tegmental area (VTA) of the rat brain. The effects of intrategmental infusions on extracellular dopamine in the ipsilateral prefrontal cortex (PFC) were recorded with a second microdialysis probe. Intrategmental infusion of tetradotoxin (1 µM), muscimol (20 µM) or baclofen (50 µM) decreased extracellular dopamine in the PFC. Infusion of N-methyl-D-aspartate (NMDA) (300 µM; 1 nM, 15 min) or kainate (50 µM, 15 min) increased extracellular dopamine in the PFC. The effects of the excitatory amino acids were suppressed by co-infusion with (+/-)-3(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (300 µM), with (+/-)-2-amin-5-phosphonopentanoic acid (500 µM), with dizocilpine maleate (500 µM) (partly) or with 6-cyano-7-nitroquinoxaline-2,3-dione (500 µM) (partly). Intrategmental infusion of carbachol (50 µM) increased extracellular dopamine in the PFC. These results provide evidence for the localization of GABAA, GABAB, NMDA, non-NMDA and cholinergic receptors on mesocortical neurons in the VTA. Intrategmental infusion of AP-5, (+/-)-2-amino-5-phosphonopentanoic acid (500 µM), of (+/-)-3(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (300 µM), of (+)3-amino-1-hydroxy-2-pyrrolidone (1 nM) and of 6-cyano-7-nitroquinoxaline-2,3dione (500 µM) decreased extracellular dopamine in the PFC. Infusion of mecamylamine, of atropine, and of 3-[[(3,4)-dichlorophenyl)methyl]propyl](diethoxymethyl) phosphonic acid into the VTA did not modify extracellular dopamine in the PFC. Infusion of bicuculline (50 µM) and that of (-)-sulpiride (50 µM) were followed by an increase in extracellular dopamine in the PFC. These data suggest that mesocortical dopamine neurons, at the level of the VTA, are tonicly excitated by glutamatergic neurons by acting on NMDA and non-NMDA receptors and are tonicly inhibited by GABA and dopamine by acting on GABAA and D2 receptors, respectively. No tonic stimulation by cholinergic neurons was detected.
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