2004 Fiscal Year Final Research Report Summary
Amino acid neural transmission and cognitive function in the animal model for drug abuse
| Project/Area Number |
15591243
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Psychiatric science
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| Research Institution | JUNTENDO UNIVERSITY |
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Principal Investigator |
SUZUKI Toshihito Juntendo University, Psychiatry, Associate Professor, 医学部, 助教授 (10196850)
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| Co-Investigator(Kenkyū-buntansha) |
OHNUMA Toru Juntendo University, Psychiatry, Assistant Professor, 医学部, 講師 (10286734)
ATAKA Hayato Juntendo University, Psychiatry, Assistant, 医学部, 助手 (60348977)
SEKI Tatsunori Juntendo University, Anatomy(II), Assistant Professor, 医学部, 講師 (20175417)
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| Project Period (FY) |
2003 – 2004
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| Keywords | coaine / phencyclidine / hippocampus / neurogenesis / sen sitization / drug abuse |
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| Research Abstract |
The disturbances of working memory and cognitive function in schizophrenia are as well as psychostimulant-related psychosis closely involved in the dysfuntions of frontal lobe and hippocampus. Those anatomical regions have neuroplasticity and long-term potential (LTP), which are unique neural mechanisms for memory or learning. In the present study, we focused on the hippocampal neurogenesis, i.e., cell proliferation and survival, in the rats following a development of behavioral sensitization Cell proliferation in the hippocampus was assessed using in-vivo labeling with 5-bromo-2'-deoxyuridine (BrdU) in adult rats. Brains were processed for triple-label immunohistofluorescence in order to examine phenotype (astrocyte or neuron) of mature BrdU positive cells. The sensitization was established by repeated administration of cocaine or phencyclidine. Behavioral abnormalities were assessed according to a quantitative analysis of locomotor and a score of stereotypy.
The locomotor activities a
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nd mean scores for stereotypies in the psychostimulants-treated groups were increased significantly compared to the control group on days 1, 5, 10, 14. The degrees of weaving and ataxia observed in the phencyclidine-treated rats were gradually decreased with injections of psychostimulants. The cell proliferation was unchanged 24 hr after a single administration of cocaine or phencyclidine, compared to the controls, respectively. Repeated administration of these psychostimulants for 14 days decreased cell proliferation by 23-26 %, compared to the controls. However, the reduction of cell proliferation was returned to the control level 1 week following repeated administration of psychostimulants. At 4 weeks after an injection of BrdU subsequent to repeated administration, cell differentiation of newly formed cells was not altered. These data imply that the regulation of hippocampal cell proliferation by cocaine or phencyclidine may be involved in the development of certain symptoms of addiction, such as cognitive impairment and acquisition of behavioral sensitization. Less
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