The pharmacology of mesolimbic dopamine neurons: a dual-probe microdialysis study in the ventral tegmental area and nucleus accumbens of the rat brain.
Receptor-specific compounds were applied by retrograde microdialysis to the ventral tegmental area (VTA) of the rat brain. The effect of the intrategmental infusions on extracellular dopamine in the ipsilateral nucleus accumbens were recorded with a second microdialysis probe. Intrategmental infusion of muscimol (10-40 microM) or baclofen (50 microM) decreased extracellular dopamine in the nucleus accumbens. Intrategmental infusion of NMDA (1 mM, 15 min) or kainate (50 microM, 15 min) increased extracellular dopamine in the nucleus accumbens. The effects of the excitatory amino acids were suppressed by co-infusion of MK-801 (1 MM), (+)-3-amino-1-hydroxy-2-pyrrolidone [(+)-HA966; 1 mM], (+/-)-3(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP; 100 microM), and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX;300 microM). Intrategmental infusion of of carbachol (50 microM) increased extracellular dopamine in the nucleus accumbens. These results provide evidence for localization of GABAA, GABAB NMDA, non-NMDA, and cholinergic receptors on dopamine neurons in the VTA. Infusions of CPP, (+)-MK-801, (+)-HA966, CNQX, mecamylamine, atropine, or 3-[[(3,4-dichlorophenyl)methyl]propyl](diethoxymethyl) phosphonic acid (CGP 52432) into the VTA did not modify extracellular dopamine in the nucleus accumbens. Infusion of bicuculline (50 microM) and (-)-sulpiride (50 microM) was followed by an increase in extracellular dopamine in the nucleus accumbens. These data suggest that dopamine neurons in the VTA are tonically inhibited by GABA and dopamine by acting on GABAA, and D2 receptors, respectively. A tonic stimulation by glutamatergic or cholinergic neurons was not detected. Finally, results on A10 neurons are compared with earlier data on A9 neurons. A striking difference was found in that GABAA-dopamine interactions are indirect in the substantia nigra and direct in the VTA.
Westerink
B H
BH
Department of Medicinal Chemistry, University Center for Pharmacy, University of Groningen, The Netherlands.
Kwint
H F
HF
deVries
J B
JB
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D009118:Muscimol / Q000494:pharmacology*; D016202:N-Methylaspartate / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D017557:Ventral Tegmental Area / Q000187:drug effects*
D009118:Muscimol; D016202:N-Methylaspartate; D001418:Baclofen; D004298:Dopamine; D001640:Bicuculline