| Project/Area Number |
16591166
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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 | Jikei University School of Medicine |
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Principal Investigator |
MIYATA Hisatsugu Jikei University School of Medicine, Department of Medicine, Associate Professor (70239416)
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| Co-Investigator(Kenkyū-buntansha) |
KOGA Minako The Jikei University, Department of Medicine, Assistant Professor (30277032)
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| Project Period (FY) |
2004 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,750,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥150,000)
Fiscal Year 2007: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2006: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2005: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2004: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | nicotine / conditioned place preference / intracranial self-stimulation / conditioned stimulus / brain reward system / medial forebrain bundle / lateral hypothalamus / rat / ドパミンD3受容体部分刺激薬 / 条件づけ / 環境刺激 / 内側前頭前野 / 腹側被蓋野 / 扁桃体 / 側坐核 / 自発運動量 / ドパミン / 6-ハイドロキシドパミン |
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| Research Abstract |
The purpose of the present study was to investigate the involvement of environmental stimuli associated with nicotine (NCT) in NCT dependence. In a conditioned place preference (CPP) paradigm, NCT-associated environmental stimuli maintained a place preference for NCT up to 6 months. Destruction of DA system with 6-OHDA in the basolateral amygdala (AMY) and ventral tegmental area (VTA) decreased a place preference for NCT elicited by NCT-associated environmental stimuli. Disruption of CPPs elicited by NCT-associated environmental stimuli in rats treated with 6-OHDA was reversed by administration of the training dose of NCT (0.4 mg/kg, s.c.). In an intracranial self-stimulation (ICSS) paradigm, NCT-associated environmental stimuli decreased lateral hypothalamus ICSS thresholds, whereas NCT-unrelated environmental stimuli did not. BP 897, a D3 partial agonist, administered prior to the conditioning sessions with NCT tended to block an ability of NCT-associated environmental stimuli to decrease medial forebrain bundle ICSS thresholds. These results indicate 1) the environmental stimuli associated with NCT function as powerful cues to maintain NCT-seeking behavior through stimulating a brain reward system, 2) the AMY and the VTA DA system are involved in NCT-seeking behavior elicited by the environmental stimuli associated with NCT, 3) BP 897 is a candidate as a new drug to prevent NCT-seeking behavior by blocking an association between NCT and the environmental stimuli.
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