Startseite Medizin Histamine H3 receptor antagonists display antischizophrenic activities in rats treated with MK-801
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Histamine H3 receptor antagonists display antischizophrenic activities in rats treated with MK-801

  • Danish Mahmood EMAIL logo , Mohd Akhtar , Kausar Jahan und Dipanjan Goswami
Veröffentlicht/Copyright: 18. April 2016
Journal of Basic and Clinical Physiology and Pharmacology
Aus der Zeitschrift Journal of Basic and Clinical Physiology and Pharmacology Band 27 Heft 5

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.

Keywords: ciproxifan; clobenpropit; histamine H3 receptor; locomotor hyperactivity; MK-801

Acknowledgments:

The authors acknowledge and thank the Department of Science and Technology, New Delhi, India, for providing financial support for the chemicals and instruments.

  1. Author contributions: Dr. Danish Mahmood designed the research protocol for the study and carried out all the preclinical studies. Dr. Kausar Jahan helped in writing the manuscript and collecting of literatures. Dr. Dipanjan Goswami conducted the LC-MS/MS for estimation of neurotransmitter. Dr. Mohd Akhtar acted as the main supervisor of the study and designed the protocol and guided the entire research work. All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: Department of Science and Technology, Government of India, and DST Fellowship.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

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Received: 2015-5-7
Accepted: 2016-3-5
Published Online: 2016-4-18
Published in Print: 2016-9-1

©2016 Walter de Gruyter GmbH, Berlin/Boston

Artikel in diesem Heft

  1. Frontmatter
  2. Review
  3. Non-diabetic clinical applications of insulin
  4. Mini Review
  5. Monophasic action potential recordings: which is the recording electrode?
  6. Behavior and Neuroprotection
  7. Histamine H3 receptor antagonists display antischizophrenic activities in rats treated with MK-801
  8. Nephroprotective effect of β-sitosterol on N-diethylnitrosamine initiated and ferric nitrilotriacetate promoted acute nephrotoxicity in Wistar rats
  9. Reproduction
  10. Implication of caffeine consumption and recovery on the reproductive functions of adult male Wistar rats
  11. Cardiovascular Function
  12. Cosmic ray (neutron) activity and air pollution nanoparticles – cardiovascular disease risk factors – separate or together?
  13. Oxidative Stress
  14. Nephrotoxicity of sodium valproate and protective role of L-cysteine in rats at biochemical and histological levels
  15. Effect of protocatechuic acid on lipid profile and DNA damage in D-galactosamine-induced hepatotoxic rats
  16. Oral administration of green plant-derived chemicals and antioxidants alleviates stress-induced cellular oxidative challenge
  17. Phytotherapy
  18. Scientific evidence of plant with a rapid-onset and sustained antidepressant effect in a chronic model of depression: Mallotus oppositifolius
  19. Anxiolytic-like effect of the leaves of Pseudospondias microcarpa (A. Rich.) Engl. in mice
  20. Comparative phytochemical profiling of Clerodendrum infortunatum with some selected medicinal plants predominant in the Sub-Himalayan region of West Bengal
https://doi.org/10.1515/jbcpp-2015-0045
Schlagwörter für diesen Artikel
ciproxifan; clobenpropit; histamine H3 receptor; locomotor hyperactivity; MK-801

Artikel in diesem Heft

  1. Frontmatter
  2. Review
  3. Non-diabetic clinical applications of insulin
  4. Mini Review
  5. Monophasic action potential recordings: which is the recording electrode?
  6. Behavior and Neuroprotection
  7. Histamine H3 receptor antagonists display antischizophrenic activities in rats treated with MK-801
  8. Nephroprotective effect of β-sitosterol on N-diethylnitrosamine initiated and ferric nitrilotriacetate promoted acute nephrotoxicity in Wistar rats
  9. Reproduction
  10. Implication of caffeine consumption and recovery on the reproductive functions of adult male Wistar rats
  11. Cardiovascular Function
  12. Cosmic ray (neutron) activity and air pollution nanoparticles – cardiovascular disease risk factors – separate or together?
  13. Oxidative Stress
  14. Nephrotoxicity of sodium valproate and protective role of L-cysteine in rats at biochemical and histological levels
  15. Effect of protocatechuic acid on lipid profile and DNA damage in D-galactosamine-induced hepatotoxic rats
  16. Oral administration of green plant-derived chemicals and antioxidants alleviates stress-induced cellular oxidative challenge
  17. Phytotherapy
  18. Scientific evidence of plant with a rapid-onset and sustained antidepressant effect in a chronic model of depression: Mallotus oppositifolius
  19. Anxiolytic-like effect of the leaves of Pseudospondias microcarpa (A. Rich.) Engl. in mice
  20. Comparative phytochemical profiling of Clerodendrum infortunatum with some selected medicinal plants predominant in the Sub-Himalayan region of West Bengal
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