NMDA receptors are not involved in the MK-801-induced increase of striatal dopamine release in rat: a microdialysis study.
Brain microdialysis and high-performance liquid chromatography with electrochemical detection were utilized to study the effect of the selective non-competitive NMDA antagonist MK-801 (dizocilpine) on striatal dopamine (DA) release in the anesthetized rat. Perfusion of 100 microM and 300 microM (+/-)-MK-801 through the probe did not significantly change the basal release of DA. These results suggest that excitatory amino acids do not exert a tonic excitatory influence on striatal DA release through NMDA receptors. 1 mM and 3 mM (+/-)-MK-801 caused a significant increase (398% and 580%, respectively), while there was no change in the level of dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). To clarify the mechanism of the (+/-)-MK-801-induced increase, the differential effect of its enantiomers (the active (+)-MK-801 and the less active (-)-MK-801) was determined. There was no difference in the action of these compounds: both drugs increased the striatal DA release with the same efficacy. Our data suggest that the MK-801-induced increase of striatal DA release is not an NMDA receptor-mediated effect.
Kiss
J P
JP
Department of Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest.
Tóth
E
E
Lajtha
A
A
Vizi
E S
ES
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D004563:Electrochemistry; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D013237:Stereoisomerism
D016194:Receptors, N-Methyl-D-Aspartate; D015102:3,4-Dihydroxyphenylacetic Acid; D016291:Dizocilpine Maleate; D004298:Dopamine; D006719:Homovanillic Acid