Eating-induced dopamine release from mesolimbic neurons is mediated by NMDA receptors in the ventral tegmental area: a dual-probe microdialysis study.
This study was aimed at identifying the neuronal pathways that mediate the eating-induced increase in the release of dopamine in the nucleus accumbens of the rat brain. For that purpose, a microdialysis probe was implanted in the ventral tegmental area and a second probe was placed in the ipsilateral nucleus accumbens. Receptor-specific compounds acting on GABA(A) (40 microM muscimol; 50 microM bicuculline), GABA(B) (50 microM baclofen), acetylcholine (50 microM carbachol), NMDA [30 microM (+/-)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP)], and non-NMDA [300 microM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)] receptors were infused into the ventral tegmental area by retrograde dialysis, whereas extracellular dopamine was recorded in the ipsilateral nucleus accumbens. Intrategmental infusion of muscimol or baclofen decreased extracellular dopamine in the ipsilateral nucleus accumbens; CPP and CNQX were without effect, and bicuculline and carbachol increased dopamine release. During infusion of the various compounds, food-deprived rats were allowed to eat for 10 min. The infusions of muscimol, bicuculline, baclofen, carbachol, and CNQX did not prevent the eating-induced increase in extracellular dopamine in the nucleus accumbens. However, during intrategmental infusion of CPP, the eating-induced increase in extracellular dopamine in the nucleus accumbens was suppressed. These results indicate that a glutamatergic projection to the ventral tegmental area mediates, via an NMDA receptor, the eating-induced increase in dopamine release from mesolimbic dopamine neurons.
Westerink
B H
BH
Department of Medicinal Chemistry, University Centre for Pharmacy, University of Groningen, The Netherlands.
Kwint
H F
HF
de Vries
J B
JB
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D004435:Eating / Q000502:physiology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D008297:Male; D017551:Microdialysis; D009118:Muscimol / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000378:metabolism*; D010277:Parasympathomimetics / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D013681:Tegmentum Mesencephali / Q000187:drug effects / Q000378:metabolism*
D018691:Excitatory Amino Acid Antagonists; D018755:GABA Agonists; D018756:GABA Antagonists; D010277:Parasympathomimetics; D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; D009118:Muscimol; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D002217:Carbachol; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; D001418:Baclofen; D004298:Dopamine; D001640:Bicuculline