Study of mechanism of action of antipsychotic drugs in the animal model of schizophrenia

The effect of non-competitive NMDA receptor antagonist phencyclidine(PCP)on the binding to dopamine D I D 22 ii D2 and serotonin 5-HT I D22AⅡD2 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 I D 22 I D 2 and 5-HT I D 22 D 2 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 I D 22A ii receptors in both saline-and PCP(5 mg/kg)-treated rats。However，stress-induced changes in the D I D 22 I D 2 and 5-HT I D 22A D 2 receptors 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 D 22…More D2and5-HT，D22A，D2receptors 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 I D 22 ii 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 decreased5-HT I D 22A齐埃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 I D 22 ii D 2 and 5-HT I D 22A D 2 receptors using N-ethoxycarbony 1-2-ethoxy-1，2-dihydroquinoline(EEDQ)suggested that high occupation of 5-HT I D 22 A I D 2 receptors with lower D I D 22 D 2 receptor occupancy might be involved in the absence of up-regulation of D I D 22 receptors with lower D D 22 D 2 receptors after drchronic treatment with sypatical syypotic syipotic systemical systic systemitic systatic.Less：Less

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 … More 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