Effect of systemic L-DOPA administration on extracellular kynurenate levels in the rat striatum.
Dopaminergic stimulation, caused by direct dopamine receptor agonists or by indirectly acting agents such as d-amphetamine or methylphenidate, causes a functionally significant decrease in the concentration of kynurenate (KYNA), an astrocyte-derived endogenous antagonist of both N-methyl-D-aspartate (NMDA) and alpha7 nicotinic acetylcholine receptors, in the rat brain. The present study was designed to examine if this effect can be duplicated by the systemic administration of dopamine's bioprecursor L-DOPA. Experiments were conducted in unanesthetized rats, and the extracellular levels of KYNA were determined in striatal microdialysate samples. L-DOPA caused a dose-dependent, transient reduction in striatal KYNA, reaching a nadir of -37.5% 1.5 h after the administration of 200 mg/kg of the drug. This effect was abolished in animals with a 6-hydroxydopamine-induced lesion of the nigrostriatal pathway, but was not influenced by a prior striatal quinolinate lesion. These data confirm the dopaminergic control of striatal KYNA formation and suggest that the interactions are mediated by astrocytic dopamine receptors. This modulation of striatal KYNA levels might provide a link between dopaminergic, glutamatergic and cholinergic neurotransmission in the normal and diseased striatum.
Wu
H-Q
HQ
Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD, USA.
Rassoulpour
A
A
Schwarcz
R
R
D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D007736:Kynurenic Acid / Q000378:metabolism*; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D017072:Neostriatum / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009498:Neurotoxins / Q000494:pharmacology; D016627:Oxidopamine / Q000494:pharmacology; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D017378:Quinolinic Acid / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D064569:alpha7 Nicotinic Acetylcholine Receptor
C579165:Chrna7 protein, rat; D009498:Neurotoxins; D011954:Receptors, Dopamine; D016194:Receptors, N-Methyl-D-Aspartate; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D007980:Levodopa; D016627:Oxidopamine; D017378:Quinolinic Acid; D007736:Kynurenic Acid; D004298:Dopamine