title: Olanzapine and clozapine but not haloperidol reverse subchronic phencyclidine-induced functional hyperactivity of N-methyl-D-aspartate receptors in pyramidal cells of the rat medial prefrontal cortex.
abstract: In the present study, we have investigated and compared the ability of olanzapine, clozapine and haloperidol to modulate phencyclidine (PCP)-induced effect in pyramidal cells of the medial prefrontal cortex (mPFC) of rats using the techniques of intracellular recording and voltage-clamp. Subchronic treatment of rats with PCP (2 mg/kg, b.i.d., 7 days, 48-60 h withdrawal) produced: (1) a depolarized resting membrane potential, a decrease of slow after hyperpolarization (sAHP) and spike frequency adaptation, (2) a shift of the concentration response curve of N-methyl-D-aspartate (NMDA), but not (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), to the left, (3) a decrease of the paired pulse facilitation (PPF) with an increase of excitatory postsynaptic current variance (EPSC variance), and (4) a reduction of the blockade of NMDA response by in vitro application of PCP. Repeated treatment with either olanzapine or clozapine, but not haloperidol, completely prevented the aforementioned subchronic PCP-induced effects. The present results indicate that the atypical antipsychotic drugs (APDs) clozapine and olanzapine share a common property in preventing subchronic PCP-induced functional hyperactivity of NMDA receptors.
authors.affiliation: Department of Psychiatry and Behavioral Science, Stony Brook University, Stony Brook, NY 11794-8790, USA. INinan@NKI.RFMH.ORG
authors.forename: I
authors.initials: I
authors.lastname: Ninan
authors.forename: K E
authors.initials: KE
authors.lastname: Jardemark
authors.forename: R Y
authors.initials: RY
authors.lastname: Wang
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001569:Benzodiazepines; D003024:Clozapine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D016202:N-Methylaspartate / Q000008:administration & dosage / Q000494:pharmacology; D000077152:Olanzapine; D018408:Patch-Clamp Techniques; D010622:Phencyclidine / Q000008:administration & dosage; D010890:Pirenzepine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D017966:Pyramidal Cells / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000502:physiology; D012559:Schizophrenia / Q000139:chemically induced / Q000503:physiopathology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D014150:Antipsychotic Agents; D018690:Excitatory Amino Acid Agonists; D016194:Receptors, N-Methyl-D-Aspartate; D001569:Benzodiazepines; D010890:Pirenzepine; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D010622:Phencyclidine; D003024:Clozapine; D006220:Haloperidol; D000077152:Olanzapine