The effect of phencyclidine on the basal and high potassium evoked extracellular GABA levels in the striatum of freely-moving rats: an in vivo microdialysis study.
The effect of phencyclidine (PCP) on the gamma-aminobutyric acid-ergic (GABAergic) transmission in the striatum of freely-moving rats was investigated using an in vivo microdialysis. The high potassium (100 mM) increased the extracellular GABA level to 4000% of the basal level. Although the basal GABA level in the striatal dialysate did not show either calcium dependency or tetrodotoxin (TTX) sensitivity, the high potassium evoked GABA level was reduced by 82% under calcium-free conditions (with 12.5 mM magnesium) and by 54% in the presence of 10 microM TTX. The systemic administration of PCP (7.5 mg/kg) or the local perfusion of PCP (100 microM and 1 mM) significantly inhibited the high potassium evoked GABA release in the rat striatum. The local perfusion of MK-801 (10 microM and 100 microM), a more potent and selective N-methyl-D-aspartate (NMDA) receptor antagonist, also inhibited the high potassium evoked striatal GABA release. These drugs did not show any significant effect on the basal extracellular GABA level. NMDA (1 mM) either partly or completely blocked the effect of PCP (1 mM) or MK-801 (100 microM) on the high potassium evoked striatal GABA release. On the other hand, nomifensine (100 microM), a dopamine uptake blocker, did not show any effect on the high potassium evoked GABA release. These results suggest that PCP inhibited the striatal GABAergic neuronal transmission through its antagonism of the NMDA receptor.
Hondo
H
H
Laboratory of Neurochemistry, Hizen National Mental Hospital, Kanzaki Saga, Japan.
Nakahara
T
T
Nakamura
K
K
Hirano
M
M
Uchimura
H
H
Tashiro
N
N
D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology; D008297:Male; D017551:Microdialysis; D016202:N-Methylaspartate / Q000494:pharmacology; D017072:Neostriatum / Q000187:drug effects*; D009627:Nomifensine / Q000494:pharmacology; D010622:Phencyclidine / Q000494:pharmacology*; D011188:Potassium / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000037:antagonists & inhibitors; D013779:Tetrodotoxin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000187:drug effects* / Q000378:metabolism
D016194:Receptors, N-Methyl-D-Aspartate; D009627:Nomifensine; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D010622:Phencyclidine; D011188:Potassium