| Project/Area Number |
14570095
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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 |
General pharmacology
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| Research Institution | Kawasaki Medical School |
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Principal Investigator |
KATSURA Masashi Kawasaki Medical School, School of Medicine, Assistant Professor, 医学部, 講師 (80204452)
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| Co-Investigator(Kenkyū-buntansha) |
WATANABE Satoru Kawasaki Medical School, School of Medicine, Assistant Professor, 医学部, 講師 (90069055)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2003: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2002: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Drug dependence / Abused drugs / Diazepam binding inhibitor / Cerebral cortical neurons / Calcium influx / Up-regulation / Protein phosphorvlation / High voltage-gated calcium channels / カルモデュリン / 電位依存性カルシウムチャネル / 大脳皮質神経細胞 / アルコール / モルヒネ / ニコチン |
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| Research Abstract |
Neuropharmacological mechanisms underlying development of drug dependence and withdrawal syndrome remain unclear at present. Several clinical features of withdrawal syndrome are considered to be common(i.e. anxiety) among patients with drug dependence induced by different drugs of abuse. In the present study, we have investigated functional alterations in diazepam binding inhibitor(DBI), an endogenous anxiogenic neuropeptide, in drug dependence and its withdrawal symptom. The levels of DBI protein and its mRNA significantly increased in the brains from mice dependent on alcohol, nicotine and morphine, and abrupt cessation of these drugs facilitated further increase in DBI expression. Similar patterns of DBI expression were observed in the neurons after sustained exposure to these drugs and its removal from culture medium. Sustained exposure of the neurons to abused drugs significantly increased the KC1(30mM)-induced[^<45>Ca^<2+>]influx and enhanced expression of α1 and α2/δ1 subunits for L-type high voltage-gated Ca^<2+> channels(HVCCs). In addition, the increase in DBI expression by drugs of abuse was completely blocked by L-type HVCC inhibitors. However, the increases in expression of L-type HVCCs after sustained exposures to drugs of abuse were not abolished by inhibitors for protein kinase A,C and CaM kinase II, respectiverly. These data indicate that up-regulation of L-type HVCCs, which causes increase in DBI expression, is considered to be a common biochemical process in drug dependence induced by different drugs of abuse.
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