Regulation of the mesocorticolimbic dopamine system by glutamic acid receptor subtypes.
Glutamic acid and excitatory amino acids specific for the glutamate receptor subtypes were microinjected into the A10 region of the rat. Glutamate produced an increase in motor behavior that was antagonized by pretreatment with the dopamine D2 receptor antagonist, haloperidol. This motor stimulant effect was produced by kainate, but not by N-methyl-D-aspartate (NMDA) or quisqualic acid. By using in vivo dialysis it was found that dopamine release in the nucleus accumbens and locomotor activity were enhanced by glutamate injection into the A10 region. Whereas glutamate was found to increase the postmortem concentration of dopamine metabolites in the medial prefrontal cortex, nucleus accumbens and A10 region, NMDA selectively increased dopamine metabolism in the prefrontal cortex, and kainate produced increases in the nucleus accumbens and A10 region. When glutamate and the NMDA receptor antagonist, 3-[(+/-)-2-carboxypiperazine-4-yl)propyl-1-phosphonic acid (CPP) were coadministered, CPP selectively abolished the effect of glutamate on medial prefrontal cortical dopamine metabolites. A physiological role for the NMDA receptor modulation of A10 dopamine neurons was shown by intra-A10 pretreatment with CPP antagonism of mild footshock-induced increase in dopamine metabolites in the prefrontal cortex. These data argue that glutamate is a regulatory transmitter of A10 dopamine neurons, and that the NMDA receptor subtype modulates neurons projecting to the prefrontal cortex whereas the kainate subtype modulates mesoaccumbens neurons.
Kalivas
P W
PW
Department of Veterinary Comparative Anatomy, Pharmacology and Physiology, Washington State University, Pullman.
Duffy
P
P
Barrow
J
J
D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001679:Biogenic Amines / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000473:pathology; D001923:Brain Chemistry / Q000187:drug effects; D004298:Dopamine / Q000502:physiology*; D005971:Glutamates / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000502:physiology*
D000596:Amino Acids; D001679:Biogenic Amines; D004298:Dopamine; D005971:Glutamates; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter