MK801 suppresses the L-DOPA-induced increase of glutamate in striatum of hemi-Parkinson rats.
In vivo microdialysis in freely moving rats was used to investigate the influence of the indirect dopamine receptor agonist levodopa (L-DOPA), alone and combined with the N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine (MK801), on extracellular glutamate levels in the striatum of intact and 6-hydroxydopamine-lesioned rats. L-DOPA (25 mg/kg i.p. after benserazide 10 mg/kg i.p.) increased extracellular glutamate levels in the striatum of both intact and dopamine-depleted rats. A prior injection of MK801 (0.1 and 1.0 mg/kg i.p.) did not alter the L-DOPA-induced glutamate release in the striatum of intact rats. In contrast, the L-DOPA-induced increase in glutamate in the striatum of 6-hydroxydopamine-lesioned rats was suppressed by MK801 (0.1 mg/kg i.p.). The data presented here suggest that NMDA receptors do not play a role in the L-DOPA-induced increase in striatal glutamate in intact rats but are involved in the glutamate release in the dopamine-depleted striatum. The suppression of this increase by prior administration of MK801 could represent a neuroprotective effect.
Jonkers
Nadine
N
Department of Pharmaceutical Chemistry and Drug Analysis, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium.
Sarre
Sophie
S
Ebinger
Guy
G
Michotte
Yvette
Y
D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D003342:Corpus Striatum / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism*; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013565:Sympatholytics; D009435:Synaptic Transmission / Q000187:drug effects
D000978:Antiparkinson Agents; D018691:Excitatory Amino Acid Antagonists; D013565:Sympatholytics; D018698:Glutamic Acid; D007980:Levodopa; D016291:Dizocilpine Maleate; D016627:Oxidopamine