Intra-striatal phencyclidine inhibits N-methyl-D-aspartic acid-stimulated increase in glutamate levels of freely moving rats.
1. The authors investigated the effect of local phencyclidine (phenylcyclohexylpiperidine, PCP) on extracellular levels of glutamate and gamma-amino butyric acid (GABA) in rat striatum using in vivo microdialysis. 2. Intrastriatal infusion of PCP (1 mM) via a microdialysis probe did not alter the basal extracellular levels of either glutamate or GABA. Addition of N-methyl-D-aspartic acid (NMDA; 0.2, 0.5 and 1 mM) to the perfusion medium resulted in a dose-dependent increase in extracellular levels of glutamate. 3. Intrastriatal infusion of tetrodotoxin (0.1, 1, 10 microM), a highly selective blocker of voltage-dependent sodium channels, significantly attenuated the NMDA-stimulated release of glutamate, suggesting that NMDA-evoked release of glutamate originated from the neuronal pool and that the increase of striatal glutamate level was regulated indirectly via NMDA receptors. 4. The NMDA-induced release of glutamate was reduced significantly by pretreatment with local PCP (1 mM). Dizocilpine (MK801; 0.2 mM), a non-competitive NMDA antagonist, completely inhibited the NMDA-stimulated release of glutamate. 5. These results suggest that, in the striatum, PCP inhibits corticostriatal glutamatergic neurotransmission by inhibiting the release of glutamate probably via postsynaptic NMDA receptors.
Yamamoto
Y
Y
Hyogo Institute for Aging Brain and Cognitive Disorders, Himeji, Japan.
Kakigi
T
T
Maeda
K
K
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D018698:Glutamic Acid / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology*; D010622:Phencyclidine / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000187:drug effects / Q000378:metabolism
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D010622:Phencyclidine