title: Histamine H3 receptor antagonists display antischizophrenic activities in rats treated with MK-801.
abstract: BACKGROUND
  Animal models based on N-methyl-d-aspartate receptor blockade have been extensively used for schizophrenia. Ketamine and MK-801 produce behaviors related to schizophrenia and exacerbated symptoms in patients with schizophrenia, which led to the use of PCP (phencyclidine)- and MK-801 (dizocilpine)-treated animals as models for schizophrenia.
  
  
  METHODS
  The study investigated the effect of subchronic dosing (once daily, 7 days) of histamine H3 receptor (H3R) antagonists, ciproxifan (CPX) (3 mg/kg, i.p.), and clobenpropit (CBP) (15 mg/kg, i.p.) on MK-801 (0.2 mg/kg, i.p.)-induced locomotor activity and also measured dopamine and histamine levels in rat's brain homogenates. The study also included clozapine (CLZ) (3.0 mg/kg, i.p.) and chlorpromazine (CPZ) (3.0 mg/kg, i.p.), the atypical and typical antipsychotic, respectively.
  
  
  RESULTS
  Atypical and typical antipsychotic was used to serve as clinically relevant reference agents to compare the effects of the H3R antagonists. MK-801 significantly increased horizontal locomotor activity, which was reduced with CPX and CBP. MK-801-induced locomotor hyperactivity attenuated by CPX and CBP was comparable to CLZ and CPZ. MK-801 raised striatal dopamine level, which was reduced in rats pretreated with CPX and CBP. CPZ also significantly lowered striatal dopamine levels, although the decrease was less robust compared to CLZ, CPX, and CBP. MK-801 increased histamine content although to a lesser degree. Subchronic treatment with CPX and CBP exhibited further increased histamine levels in the hypothalamus compared to MK-801 treatment alone. Histamine H3 receptor agonist, R-α methylhistamine (10 mg/kg, i.p.), counteracted the effect of CPX and CBP.
  
  
  CONCLUSIONS
  The present study shows the positive effects of CPX and CBP on MK-801-induced schizophrenia-like behaviors in rodents.
authors.forename: Danish
authors.initials: D
authors.lastname: Mahmood
authors.forename: Mohd
authors.initials: M
authors.lastname: Akhtar
authors.forename: Kausar
authors.initials: K
authors.lastname: Jahan
authors.forename: Dipanjan
authors.initials: D
authors.lastname: Goswami
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D006632:Histamine / Q000378:metabolism; D054828:Histamine H3 Antagonists / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology; D008761:Methylhistamines / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012559:Schizophrenia / Q000188:drug therapy* / Q000378:metabolism; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D014150:Antipsychotic Agents; D054828:Histamine H3 Antagonists; D007093:Imidazoles; D008761:Methylhistamines; D016194:Receptors, N-Methyl-D-Aspartate; C115705:ciproxifan; C069357:alpha-methylhistamine; D016291:Dizocilpine Maleate; D006632:Histamine; D013890:Thiourea; C086108:clobenpropit