| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1999: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1998: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1997: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Research Abstract |
The effect of non-competitive NMDA receptor antagonist phencyclidine (PCP) on the binding to dopamine DィイD22ィエD2 and serotonin 5-HTィイD22AィエD2 receptor was examined in the rat striatum and frontal cortex, respectively. Neither acute or 3-week treatment with 5 mg/kg PCP had any significant effect on DィイD22ィエD2 and 5-HTィイD22AィエD2 receptors. Acute or 8-day footshock stress (1 series: 2.5 mA for 30 sec, randam interval; mean 30 sec, 30 times) did not significantly affect the D2 and 5-HTィイD22AィエD2 receptors in both saline- and PCP (5 mg/kg)-treated rats. However, stress-induced changes in the DィイD22ィエD2 and 5-HTィイD22AィエD2receptors were different, although not significantly, between the two groups. It is possible that PCP treatment may influence the dopaminergic and serotonergic compensatory systems to stress.
The effects of 3-week treatment with a atypical antipsychotic drug chlorpromazine and three typical antipsychotic drugs (risperidone, olanzapine and perospirone) on the binding to DィイD22
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ィエD2 and 5-HTィイD22AィエD2 receptors were examined in the rat striatum and frontal cortex, respectively. Subchronic treatment with chlorpromazine (10 mg/kg) and perospirone (1 mg/kg) significantly increased DィイD22ィエD2 receptors, while no increase was observed with lower dose of chlorpromazine (5 mg/kg), perospirone (0.1 mg/kg), risperidone (0.25, 0.5 mg/kg) or olanzapine (1, 2 mg/kg). On the other hand, 3-week administration of chlorpromazine (5, 10 mg/kg)and olanzapine (1, 2 mg/kg) significantly decreased 5-HTィイD22AィエD2 receptors, but risperidone (0.25, 0.5 mg/kg) or perospirone (0.1, 1 mg/kg) had no effect. The measurement of in vivo drug occupation for DィイD22ィエD2 and 5-HTィイD22AィエD2 receptors using N-ethoxycarbony1-2-ethoxy-1, 2-dihydroquinoline (EEDQ) suggested that high occupation of 5-HTィイD22AィエD2 receptors with lower DィイD22ィエD2 receptor occupancy might be involved in the absence of up-regulation of DィイD22ィエD2 receptors after subchronic treatment with some atypical antipsychotic drugs. Less
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