| Project/Area Number |
02670508
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Psychiatric science
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| Research Institution | Tohoku University |
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Principal Investigator |
SATO Mitsumoto Tohoku University School of Medicine Department of Psychiatry Professor, 医学部, 教授 (70033321)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIDA Sumiko Tohoku University Hospital Department of Psychiatry Staff psychiatrist, 医学部附属病院, 医員
NUMACHI Yohtaro Tohoku University Hospital Department of Psychiatry Staff psychiatrist, 医学部附属病院, 医員
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| Project Period (FY) |
1990 – 1991
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| Project Status |
Completed (Fiscal Year 1991)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1991: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1990: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | Methamphetamine psychosis / Reverse tolerance phenomenon / Dopamine uptake sites / Releasing amines / Brain distribution / Rat / Striatum / Animal models for schizophrenia / ドパミン / アイソト-プ標識メタンフェタミン |
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| Research Abstract |
In animals. a long-term behavioral sensitization to methamphetamine(MAP)has been confirmed after chronic MAP(reverse tolerance phenomenon). To date, it is suggested that lasting enhancement of MAP7induced increase in dopamine release in the striatum and nucleus accumbens relates to induction and manifestation of the brain vulnerability to psychotic relapses. According to the exchange diffusion model of Fischer and Cho(1979)regarding the MAP-induced release of dopamine at nerve terminals, it appears possible to provide a working hypothesis that brain distribution of MAP or other indirect dopamine agonists with action to dopamine transporter may be altered following repeated administration of these agents. To confirm this hypothesis. we examined a change in biodistribution of[ ^<14>C]MAP and[ ^<123>I]IMP(an analogue of MAP)in the MAP-sensitized rat brain. As for[ ^<14>C]MAP. we -demonstrated a marked increase of differential absorption ratio(DAR)in the striatum, limbic forebrain and cere
… More
bellum of the MAP-sensitized rats. These results strongly suggest that subchronic MAP administration may result a lasting change in the presynaptic cell membrane at the nerve terminal, which may in turn cause an increase in MAP uptake with subsequent increase of dopamine release in the synaptic cleft. This is our new hypothesis for a mechanism of known enhanced dopamine efflux in the striatum and nucleus accumbens when MAP was challenged to the MAP-sensitized rats. There was no difference in regional DAR of ^<123>I-IMP between the MAP-sensitized rats and control. Moreover, we examine a change in biodistribution of[ ^3H]WIN 35428(an analogue of cocaine)in the MAP-sensitized rat brain. In result, the DAR was decreased significantly in the striatum(p<0.01)and in the cerebellum(p<0.025). No change was found in the limbic forebrain. Since WIN 35428 is an analogue of cocaine, the present results suggest that subchronic MAP administration may result a lasting reduction of cocaine uptake sites, which may inhibit dopamine transporter. It is concluded that subchronic MAP may cause a lasting change in cell membrane at the dopaminergic nerve terminals of striatum and limbic forebrain, as well as nondopaminergic cells of cerebellum. Less
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