Localization of ionotropic glutamate receptors in caudate-putamen and nucleus accumbens septi of rat brain: comparison of NMDA, AMPA, and kainate receptors.
Changes in binding of selective radioligands at NMDA ([3H]MK-801), AMPA ([3H]CNQX), and kainate ([3H]kainic acid) glutamate (GLU) ionotropic receptors in rat caudate-putamen (CPu) and nucleus accumbens (NAc) were examined by quantitative autoradiography following: 1) unilateral surgical ablation of frontal cerebral cortex to remove descending corticostriatal GLU projections, 2) unilateral injection of kainic acid (KA) into CPu or NAc to degenerate local intrinsic neurons, or 3) unilateral injections of 6-hydroxydopamine (6-OH-DA) into substantia nigra to degenerate ascending nigrostriatal dopamine (DA) projections. Cortical ablation significantly decreased NMDA receptor binding in ipsilateral medial CPu (20%), and NAc (16%), similar to previously reported losses of DA D4 receptors. KA lesions produced large losses of NMDA receptor labeling in CPu and NAc (both by 52%), AMPA (41% and 45%, respectively), and kainate receptors (40% and 45%, respectively) that were similar to the loss of D2 receptors in CPu and NAc after KA injections. Nigral 6-OH-DA lesions yielded smaller but significant losses in NMDA (17%), AMPA (12%), and kainate (11%) receptor binding in CPu. The results indicate that most NMDA, AMPA, and kainate receptors in rat CPu and NAc occur on intrinsic postsynaptic neurons. Also, some NMDA, but not AMPA or kainate, receptors are also found on corticostriatal projections in association with D4 receptors; these may, respectively, represent excitatory presynaptic NMDA autoreceptors and inhibitory D4 heteroceptors that regulate GLU release from corticostriatal axons in medial CPu and NAc. Conversely, the loss of all three GLU receptor subtypes after lesioning DA neurons supports their role as excitatory heteroceptors promoting DA release from nigrostriatal neurons.
Mailman Research Center, McLean Division of Massachusetts General Hospital, Belmont 02178, USA. ftarazi@warren.med.harvard.edu
F I
FI
Tarazi
A
A
Campbell
S K
SK
Yeghiayan
R J
RJ
Baldessarini
D000818:Animals; D001345:Autoradiography; D002352:Carrier Proteins / Q000378:metabolism; D002421:Caudate Nucleus / Q000187:drug effects / Q000502:physiology*; D050483:Dopamine Plasma Membrane Transport Proteins; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D007091:Image Processing, Computer-Assisted; D007608:Kainic Acid / Q000633:toxicity; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D017072:Neostriatum / Q000187:drug effects / Q000502:physiology; D009419:Nerve Tissue Proteins; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000502:physiology; D011699:Putamen / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000187:drug effects; D017470:Receptors, Glutamate / Q000187:drug effects*; D018092:Kainic Acid Receptors / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D013378:Substantia Nigra / Q000187:drug effects / Q000502:physiology
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D018690:Excitatory Amino Acid Agonists; D007608:Kainic Acid; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate