| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1996: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1995: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Research Abstract |
In animals, a long-term behavioral sensitization (LTBS) to methamphetamine (MAP) or amphetamine (AMP) has been confirmed after subchronic administration of these central stimulants. A challenge injection of these stimulants to sensitized animals induces a significantly greater increase in dopamine (DA) release in the striatum and nucleus accumbens, which relates to induction and manifestation of the LTBS and the brain vulnerability to psychotic relapse. Since dopamine transporter (DAT) uptake MAP and AMP and release DA in exchange for them (exchange model : Fischer and Cho, 1979), DAT may play an essential role for the MAP induced LTBS.Recently, it was reported that DAT is necessary to produce LTBS and the related DA increase by DAT knockout mice (Giros, et al., 1996.). The cocaine analogue RTI 55 is one of the most potent ligand for DAT.To determine if subchronic administration of MAP produces long-lasting alterations in DAT,we examined the regional accumulation of [^<11>C] MAP in the MAP sensitized rat brain and in vitro binding of [^<125>I] RTI 55 to DAT in the striatum. Male Sprague Dawley rats received a daily injection of MAP (4 mg/kg, i.p.) for 21 days. Seven days after the last injection, rats were examined. In the MAP sensitized animals, Bmax of DAT in high affinity site significantly increased, but the accumulation of [^<11>C] MAP did not change in striatum, nucleus accumbens and cerebellum. Science, Bmax of DAT in high affinity site reflect the DAT function. These results suggest that the increased Bmax may play a part of increased DA release in LTBS.But it is difficult to explain the MAP pharmachokinetcs only by a change in striatal DAT.
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