![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 283, Issue 1, 226-234, 1997
Department of Psychiatry, State University of New York at Stony
Brook, Stony Brook, New York
The effects of the antipsychotic drugs haloperidol and clozapine on
N-methyl-D-aspartate (NMDA) and non-NMDA receptor-mediated neurotransmission were examined and compared in pyramidal cells of the
medial prefrontal cortex in rat brain slices by using the techniques of
intracellular recording and single-electrode voltage-clamp. The bath
administration of either haloperidol or clozapine produced a marked
facilitation (300-400%) of NMDA-evoked responses in a concentration-dependent manner. The EC50 values of
haloperidol and clozapine were 38 and 14 nM, respectively. At
concentrations of 
100 nM, clozapine, but not haloperidol, produced
bursts of excitatory postsynaptic potentials (EPSPs), which were
blocked by glutamate receptor antagonists, suggesting that these EPSPs were the result of increasing release of excitatory amino acids. Haloperidol, but not clozapine, produced a concentration-dependent inhibition of 
-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-induced current with an EC50 value of 37 nM.
Haloperidol significantly decreased the amplitude of EPSPs evoked by
the electrical stimulation of the forceps minor, whereas clozapine
increased the amplitude of these EPSPs. The study of current-voltage
relationship indicates that clozapine preferentially potentiates NMDA
receptor-mediated transmission, whereas haloperidol depresses the
non-NMDA receptor-mediated response, which probably obscures its
potentiating effect on NMDA receptor-mediated EPSPs.
This article has been cited by other articles:
|
|
 |
|
  J. A. Lieberman, F. P. Bymaster, H. Y. Meltzer, A. Y. Deutch, G. E. Duncan, C. E. Marx, J. R. Aprille, D. S. Dwyer, X.-M. Li, S. P. Mahadik, et al. Antipsychotic Drugs: Comparison in Animal Models of Efficacy, Neurotransmitter Regulation, and Neuroprotection Pharmacol. Rev., September 1, 2008; 60(3): 358 - 403. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. H. Large Do NMDA receptor antagonist models of schizophrenia predict the clinical efficacy of antipsychotic drugs? J Psychopharmacol, May 1, 2007; 21(3): 283 - 301. [Abstract] [PDF]
|
|
|
|
 |
|
 W.-J. Gao Acute Clozapine Suppresses Synchronized Pyramidal Synaptic Network Activity by Increasing Inhibition in the Ferret Prefrontal Cortex J Neurophysiol, February 1, 2007; 97(2): 1196 - 1208. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. R. Yang and L. Chen Targeting Prefrontal Cortical Dopamine D1 and N-Methyl-D-Aspartate Receptor Interactions in Schizophrenia Treatment Neuroscientist, October 1, 2005; 11(5): 452 - 470. [Abstract] [PDF]
|
|
|
|
 |
|
 M. Wittmann, M. J. Marino, D. A. Henze, G. R. Seabrook, and P. J. Conn Clozapine Potentiation of N-Methyl-D-aspartate Receptor Currents in the Nucleus Accumbens: Role of NR2B and Protein Kinase A/Src Kinases J. Pharmacol. Exp. Ther., May 1, 2005; 313(2): 594 - 603. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Sur, P. J. Mallorga, M. Wittmann, M. A. Jacobson, D. Pascarella, J. B. Williams, P. E. Brandish, D. J. Pettibone, E. M. Scolnick, and P. J. Conn N-desmethylclozapine, an allosteric agonist at muscarinic 1 receptor, potentiates N-methyl-D-aspartate receptor activity PNAS, November 11, 2003; 100(23): 13674 - 13679. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. G. Kinney, C. Sur, M. Burno, P. J. Mallorga, J. B. Williams, D. J. Figueroa, M. Wittmann, W. Lemaire, and P. J. Conn The Glycine Transporter Type 1 Inhibitor N-[3-(4'-Fluorophenyl)-3-(4'-Phenylphenoxy)Propyl]Sarcosine Potentiates NMDA Receptor-Mediated Responses In Vivo and Produces an Antipsychotic Profile in Rodent Behavior J. Neurosci., August 20, 2003; 23(20): 7586 - 7591. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. I. O. Myme, K. Sugino, G. G. Turrigiano, and S. B. Nelson The NMDA-to-AMPA Ratio at Synapses Onto Layer 2/3 Pyramidal Neurons Is Conserved Across Prefrontal and Visual Cortices J Neurophysiol, August 1, 2003; 90(2): 771 - 779. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. E. Duncan, S. Miyamoto, and J. A. Lieberman Chronic Administration of Haloperidol and Olanzapine Attenuates Ketamine-Induced Brain Metabolic Activation J. Pharmacol. Exp. Ther., June 1, 2003; 305(3): 999 - 1005. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Chen and C. R. Yang Interaction of Dopamine D1 and NMDA Receptors Mediates Acute Clozapine Potentiation of Glutamate EPSPs in Rat Prefrontal Cortex J Neurophysiol, May 1, 2002; 87(5): 2324 - 2336. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. C. Goff and J. T. Coyle The Emerging Role of Glutamate in the Pathophysiology and Treatment of Schizophrenia Am J Psychiatry, September 1, 2001; 158(9): 1367 - 1377. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. E. Duncan, S. Miyamoto, J. N. Leipzig, and J. A. Lieberman Comparison of the Effects of Clozapine, Risperidone, and Olanzapine on Ketamine-Induced Alterations in Regional Brain Metabolism J. Pharmacol. Exp. Ther., April 1, 2000; 293(1): 8 - 14. [Abstract] [Full Text]
|
|
|
|
|
|
V. L. Arvanov and R. Y. Wang Clozapine, But Not Haloperidol, Prevents the Functional Hyperactivity of N-Methyl-D-Aspartate Receptors in Rat Cortical Neurons Induced by Subchronic Administration of Phencyclidine J. Pharmacol. Exp. Ther., May 1, 1999; 289(2): 1000 - 1006. [Abstract] [Full Text]
|
|
 |
 |
 |
|
 |
 |
 |
