Effects of Chronic Haloperidol and Clozapine Treatment on Neurogenesis in the Adult Rat Hippocampus
It has been proposed that the therapeutic benefits of treatment with antidepressants and mood stabilizers may arise partially from their ability to stimulate neurogenesis. This study was designed to examine the effects of chronic antipsychotic treatment on cell proliferation and survival in the adul...
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Published in | Neuropsychopharmacology (New York, N.Y.) Vol. 29; no. 6; pp. 1063 - 1069 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
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New York, NY
Nature Publishing
01.06.2004
Nature Publishing Group |
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Abstract | It has been proposed that the therapeutic benefits of treatment with antidepressants and mood stabilizers may arise partially from their ability to stimulate neurogenesis. This study was designed to examine the effects of chronic antipsychotic treatment on cell proliferation and survival in the adult rat hippocampus. Haloperidol (0.05 and 2 mg/kg), clozapine (0.5 and 20 mg/kg), or vehicle were administered i.p. for 28 days, followed by bromodeoxyuridine (BrdU, 200 mg/kg, i.p.), a marker of DNA synthesis. One group of rats was killed 24 h following BrdU administration and BrdU-positive cells were quantified to assess the effects of drug treatment on cell proliferation. The remaining animals continued on antipsychotic medication for an additional 3 weeks following BrdU administration to assess the effects of antipsychotics on cell survival. Our results show that 24 h following BrdU, a low dose of clozapine (0.5 mg/kg) increased the number of BrdU-positive cells in the dentate gyrus (DG) by two-fold. Neither 20 mg/kg of clozapine nor haloperidol had any effect on cell proliferation in DG. Moreover, neither drug at either dose had an effect on the number of newly generated neurons surviving in the DG 3 weeks following BrdU administration. These preliminary findings suggest that clozapine may influence the number of cells which divide, but antipsychotics do not promote the survival of the newly generated neurons at 3 weeks after a BrdU injection. |
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AbstractList | It has been proposed that the therapeutic benefits of treatment with antidepressants and mood stabilizers may arise partially from their ability to stimulate neurogenesis. This study was designed to examine the effects of chronic antipsychotic treatment on cell proliferation and survival in the adult rat hippocampus. Haloperidol (0.05 and 2 mg/kg), clozapine (0.5 and 20 mg/kg), or vehicle were administered i.p. for 28 days, followed by bromodeoxyuridine (BrdU, 200 mg/kg, i.p.), a marker of DNA synthesis. One group of rats was killed 24 h following BrdU administration and BrdU-positive cells were quantified to assess the effects of drug treatment on cell proliferation. The remaining animals continued on antipsychotic medication for an additional 3 weeks following BrdU administration to assess the effects of antipsychotics on cell survival. Our results show that 24 h following BrdU, a low dose of clozapine (0.5 mg/kg) increased the number of BrdU-positive cells in the dentate gyrus (DG) by two-fold. Neither 20 mg/kg of clozapine nor haloperidol had any effect on cell proliferation in DG. Moreover, neither drug at either dose had an effect on the number of newly generated neurons surviving in the DG 3 weeks following BrdU administration. These preliminary findings suggest that clozapine may influence the number of cells which divide, but antipsychotics do not promote the survival of the newly generated neurons at 3 weeks after a BrdU injection. |
Author | HALIM, Nader D MCCLINTOCK, Benjamin W LIPSKA, Barbara K WEINBERGER, Daniel R WEICKERT, Cynthia Shannon |
Author_xml | – sequence: 1 givenname: Nader D surname: HALIM fullname: HALIM, Nader D organization: Clinical Brain Disorders Branch, Intramural Research Program, National Institute of Mental Health, Bethesda, MD, United States – sequence: 2 givenname: Cynthia Shannon surname: WEICKERT fullname: WEICKERT, Cynthia Shannon organization: Clinical Brain Disorders Branch, Intramural Research Program, National Institute of Mental Health, Bethesda, MD, United States – sequence: 3 givenname: Benjamin W surname: MCCLINTOCK fullname: MCCLINTOCK, Benjamin W organization: Clinical Brain Disorders Branch, Intramural Research Program, National Institute of Mental Health, Bethesda, MD, United States – sequence: 4 givenname: Daniel R surname: WEINBERGER fullname: WEINBERGER, Daniel R organization: Clinical Brain Disorders Branch, Intramural Research Program, National Institute of Mental Health, Bethesda, MD, United States – sequence: 5 givenname: Barbara K surname: LIPSKA fullname: LIPSKA, Barbara K organization: Clinical Brain Disorders Branch, Intramural Research Program, National Institute of Mental Health, Bethesda, MD, United States |
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Keywords | Rat Neuroleptic Psychotropic Dopamine antagonist Rodentia Schizophrenia Butyrophenone derivatives Clozapine Haloperidol Neurogenesis Psychosis Vertebrata Chronic Dentate gyrus Mammalia D2 Dopamine receptor Adult animal antipsychotic Hippocampus BrdU |
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SubjectTerms | Analysis of Variance Animals Antipsychotic Agents - administration & dosage Antipsychotic Agents - pharmacology Biological and medical sciences Bromodeoxyuridine - metabolism Cell Count - methods Cell Division - drug effects Cell Survival - drug effects Clozapine - administration & dosage Dizocilpine Maleate - pharmacology Dose-Response Relationship, Drug Excitatory Amino Acid Antagonists - pharmacology Fundamental and applied biological sciences. Psychology Glial Fibrillary Acidic Protein - metabolism Haloperidol - administration & dosage Haloperidol - pharmacology Hippocampus - drug effects Hippocampus - physiology Immunohistochemistry - methods Male Medical sciences Neuropharmacology Pharmacology. Drug treatments Phenotype Phosphopyruvate Hydratase - metabolism Psychology. Psychoanalysis. Psychiatry Psychology. Psychophysiology Rats Rats, Sprague-Dawley |
Title | Effects of Chronic Haloperidol and Clozapine Treatment on Neurogenesis in the Adult Rat Hippocampus |
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