Striatal glutamate release evoked in vivo by NMDA is dependent upon ongoing neuronal activity in the substantia nigra, endogenous striatal substance P and dopamine.
The aim of the present microdialysis study was to investigate whether the increase in striatal glutamate levels induced by intrastriatal perfusion with NMDA was dependent on the activation of extrastriatal loops and/or endogenous striatal substance P and dopamine. The NMDA-evoked striatal glutamate release was mediated by selective activation of the NMDA receptor-channel complex and action potential propagation, as it was prevented by local perfusion with dizocilpine and tetrodotoxin, respectively. Tetrodotoxin and bicuculline, perfused distally in the substantia nigra reticulata, prevented the NMDA-evoked striatal glutamate release, suggesting its dependence on ongoing neuronal activity and GABA(A) receptor activation, respectively, in the substantia nigra. The NMDA-evoked glutamate release was also dependent on striatal substance P and dopamine, as it was antagonized by intrastriatal perfusion with selective NK(1) (SR140333), D(1)-like (SCH23390) and D(2)-like (raclopride) receptor antagonists, as well as by striatal dopamine depletion. Furthermore, impairment of dopaminergic transmission unmasked a glutamatergic stimulation by submicromolar NMDA concentrations. We conclude that in vivo the NMDA-evoked striatal glutamate release is mediated by activation of striatofugal GABAergic neurons and requires activation of striatal NK(1) and dopamine receptors. Endogenous striatal dopamine inhibits or potentiates the NMDA action depending on the strength of the excitatory stimulus (i.e. the NMDA concentration).
Marti
Matteo
M
Department of Experimental and Clinical Medicine, Section of Pharmacology, and Neuroscience Center, University of Ferrara, Ferrara, Italy.
Manzalini
Massimiliano
M
Fantin
Martina
M
Bianchi
Clementina
C
Della Corte
Laura
L
Morari
Michele
M
D018663:Adrenergic Agents / Q000633:toxicity; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003342:Corpus Striatum / Q000166:cytology* / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018756:GABA Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D016627:Oxidopamine / Q000633:toxicity; D010880:Piperidines / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011812:Quinuclidines / Q000494:pharmacology; D020891:Raclopride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013373:Substance P / Q000378:metabolism*; D013378:Substantia Nigra / Q000166:cytology* / Q000187:drug effects; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors
D018663:Adrenergic Agents; D001552:Benzazepines; D018492:Dopamine Antagonists; D018756:GABA Antagonists; D010880:Piperidines; D011812:Quinuclidines; C085215:SR 140333; D013373:Substance P; D018698:Glutamic Acid; D020891:Raclopride; D013779:Tetrodotoxin; D016202:N-Methylaspartate; D011189:Potassium Chloride; D016627:Oxidopamine; D008274:Magnesium; D004298:Dopamine; D001640:Bicuculline