The effect of phencyclidine and DL-2-amino-5-phosphonovaleric acid on N-methyl-D-aspartic acid induced changes in extracellular concentration of dopamine and DOPAC in the rat neostriatum.
The effects of N-methyl-D-aspartic acid (NMDA) and phencyclidine (PCP) on extracellular levels of dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) in the striatum of the rat were studied using in vivo microdialysis. Intrastriatal infusion of NMDA produced a significant dose-dependent increase in extracellular DA and a decrease in concentrations of DOPAC. Whereas both 2-amino-5-phosphonovalerate (APV) and PCP antagonized the NMDA-induced increase in extracellular levels of DA, the effect on NMDA-induced changes in extracellular concentrations of DOPAC were different for the two compounds. The APV significantly attenuated the decrease in extracellular DOPAC produced by smaller concentrations of NMDA, whereas PCP did not prevent decrease in DOPAC produced by any concentrations of NMDA. Phencyclidine alone produced a dose-dependent increase in extracellular DA but had no effect on the extracellular concentration of DOPAC. This study demonstrated that PCP, at concentrations which did not produce an increase in extracellular DA, antagonized the effect of the NMDA on DA. The data also indicated that both APV and PCP antagonized the NMDA-evoked release of DA over a range of concentrations of NMDA, even though they did so by different mechanisms.
Department of Pharmacology, University of California, Los Angeles 90024.
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Marek
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Chapman
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Howard
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology*; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism*; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology*; D010622:Phencyclidine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D015102:3,4-Dihydroxyphenylacetic Acid; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; D010622:Phencyclidine; D004298:Dopamine