title: Effects of long-term treatment with the neuroleptics haloperidol, clozapine and olanzapine on immunoexpression of NMDA receptor subunits NR1, NR2A and NR2B in the rat hippocampus.
abstract: BACKGROUND
  Antagonists of the N-methyl-d-aspartate receptor (NMDA-R) are associated with symptoms of schizophrenia, leading to the hypothesis that NMDA-R hypofunction leads to the pathogenesis of disease. We evaluated the long-term effect of neuroleptic administration on the NMDA subunits via immunohistochemical analysis.
  
  
  METHODS
  Rats received olanzapine, clozapine and haloperidol before evaluation of the expression of the NR1, NR2A and NR2B subunit proteins in the hippocampal areas of the brain, via a densytometric analysis of immunoexpression in the rat hippocampus.
  
  
  RESULTS
  All of the neuroleptics examined caused a decrease in the expression of the NR1 subunit, and thus, one can assume that both olanzapine, clozapine and haloperidol decreased the number of NMDA receptors in the CA1 and CA2 areas of the brain.
  
  
  CONCLUSIONS
  A decrease in hippocampal glutamatergic signalling after long-term neuroleptic administration may cautiously explain the incomplete effectiveness of these drugs in the therapy of schizophrenia-related cognitive disturbances.
authors.affiliation: Department and Clinic of Psychiatry and Psychotherapy, Medical University of Silesia, Katowice, Poland. Electronic address: krzystanekmarek@gmail.com.
authors.forename: Marek
authors.initials: M
authors.lastname: Krzystanek
authors.affiliation: Department of Histology, Medical University of Silesia, Katowice, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Bogus
authors.affiliation: Department of Histology, Medical University of Silesia, Katowice, Poland.
authors.forename: Artur
authors.initials: A
authors.lastname: Pałasz
authors.affiliation: Department and Clinic of Neurology, Medical University of Silesia, Katowice, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Krzystanek
authors.affiliation: Manchester Immunology Group, University of Manchester, Manchester, United Kingdom.
authors.forename: John J
authors.initials: JJ
authors.lastname: Worthington
authors.affiliation: Department of Histology, Medical University of Silesia, Katowice, Poland.
authors.forename: Ryszard
authors.initials: R
authors.lastname: Wiaderkiewicz
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001569:Benzodiazepines / Q000494:pharmacology*; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism; D056651:CA2 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism; D056654:CA3 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism; D003024:Clozapine / Q000494:pharmacology*; D018891:Dentate Gyrus / Q000187:drug effects / Q000378:metabolism; D006220:Haloperidol / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects*; D008297:Male; D000077152:Olanzapine; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D014150:Antipsychotic Agents; C473649:NR1A NMDA receptor, rat; C120997:NR2A NMDA receptor; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D001569:Benzodiazepines; D003024:Clozapine; D006220:Haloperidol; D000077152:Olanzapine
keywords: Glutamate; Hippocampus; NMDA receptor; Neuroleptics