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Biphasic modulation of NMDA‐induced responses in pyramidal cells of the medial prefrontal cortex by Y‐931, a potential atypical antipsychotic drug
Author(s) -
Jardemark Kent E.,
Ai Jinglu,
Ninan Ipe,
Wang Rex Y.
Publication year - 2001
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.1086
Subject(s) - nmda receptor , phencyclidine , neuroscience , prefrontal cortex , clozapine , ampa receptor , chemistry , excitatory postsynaptic potential , olanzapine , hippocampal formation , pharmacology , psychology , schizophrenia (object oriented programming) , medicine , receptor , inhibitory postsynaptic potential , psychiatry , biochemistry , cognition
Similar to the effects produced by the atypical antipsychotic drugs (APDs) clozapine and olanzapine, Y‐931 {8‐fluoro‐12‐(4‐methylpiperazin‐1‐yl)‐6 H ‐[1]benzothieno[2,3‐ b ][1,5]benzodiazepine maleate, a purported atypical APD} effectively facilitated N‐methyl‐D‐aspartate (NMDA)‐induced, but not (±)‐α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid (AMPA)‐evoked, responses in pyramidal cells of the rat medial prefrontal cortex (mPFC). Similar to olanzapine and clozapine, the concentration–response curve of Y‐931 in these experiments was biphasic. At present, the mechanisms behind the biphasic modulatory actions of Y‐931 and olanzapine on NMDA‐induced currents in the mPFC are not clear. In addition to augmenting NMDA responses, Y‐931 prevented the phencyclidine (PCP)‐induced block of the NMDA responses and increased the amplitudes and durations of excitatory postsynaptic currents (EPSCs) evoked by electrical stimulation of the forceps minor. Overall, our findings suggest that APDs, particularly the atypical ones, share a common property in that they facilitate NMDA receptor‐mediated transmission in the mPFC and perhaps other functionally related limbic structures as well, which could be the cellular basis for their ability to alleviate some schizophrenic negative symptoms and cognitive dysfunctions. Synapse 41:294–300, 2001. © 2001 Wiley‐Liss, Inc.