Abstract

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 mM, 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 GABA_A, GABA_B, 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 mM) and of 6-cyano-7-nitroquinoxaline-2,3-dione (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 GABA_A and D₂ receptors, respectively. No tonic stimulation by cholinergic neurons was detected. The effects on mesocortical neurons and earlier published data on mesolimbic and nigrostriatal dopamine neurons are compared and discussed.