title: Extended neuroleptic administration modulates NMDA-R subunit immunoexpression in the rat neocortex and diencephalon.
abstract: BACKGROUND
  This study aimed to evaluate the effect of extended olanzapine, clozapine and haloperidol administration on NMDA-R subunit immunoexpression in the rat neocortex and diencephalon.
  
  
  METHODS
  To explore NR1, NR2A and NR2B subunit protein expression, densytometric analysis of immunohistochemically stained brain slices was performed.
  
  
  RESULTS
  Interestingly, all neuroleptics caused a downregulation of NMDA-R subunit expression in the thalamus but increased the level of NR1 in the hypothalamus. Olanzapine upregulated hypothalamic NR2A expression, while clozapine and haloperidol decreased hypothalamic levels. We observed no significant changes in NR2B immunoreactivity. None of the studied medications had significant influence on NMDA-R subunit expression in the neocortex.
  
  
  CONCLUSIONS
  Neuroleptic-induced reduction in the expression of thalamic NMDA-R subunits may play an important role in the regulation of glutamatergic transmission disorders in cortico-striato-thalamo-cortical loop in schizophrenia. A decrease in NMDA signaling in this region after long-term neuroleptic administration may also cautiously explain the incomplete effectiveness of these drugs in the therapy of schizophrenia-related cognitive disturbances.
authors.affiliation: Department and Clinic of Psychiatric Rehabilitation, School of Medicine in Katowice, 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, School of Medicine in Katowice, Medical University of Silesia,, Katowice, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Bogus
authors.affiliation: Department of Histology, School of Medicine in Katowice, Medical University of Silesia,, Katowice, Poland.
authors.forename: Artur
authors.initials: A
authors.lastname: Pałasz
authors.affiliation: Department of Histology, School of Medicine in Katowice, Medical University of Silesia,, Katowice, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Wiaderkiewicz
authors.affiliation: Department of Histology, School of Medicine in Katowice, Medical University of Silesia,, Katowice, Poland.
authors.forename: Łukasz
authors.initials: Ł
authors.lastname: Filipczyk
authors.affiliation: Department of Histology, School of Medicine in Katowice, Medical University of Silesia,, Katowice, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Rojczyk
authors.affiliation: Manchester Immunology Group, Faculty of Life Sciences, University of Manchester, Greater Manchester, UK; Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster University, Lancaster, UK.
authors.forename: John
authors.initials: J
authors.lastname: Worthington
authors.affiliation: Department of Histology, School of Medicine in Katowice, 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; D003024:Clozapine / Q000494:pharmacology; D004027:Diencephalon / Q000187:drug effects* / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D006220:Haloperidol / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects; D008297:Male; D016202:N-Methylaspartate / Q000378:metabolism*; D019579:Neocortex / Q000187:drug effects* / Q000378:metabolism; D000077152:Olanzapine; D021122:Protein Subunits / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D014150:Antipsychotic Agents; D021122:Protein Subunits; D001569:Benzodiazepines; D016202:N-Methylaspartate; D003024:Clozapine; D006220:Haloperidol; D000077152:Olanzapine
keywords: NMDA receptor; diencephalon; glutamate; neocortex; neuroleptics