open access

https://doi.org/10.11501/3145399

https://hdl.handle.net/2115/51570

Effects of serotonergic drugs on the up-regulation of dopamine D2 receptors induced by haloperidol in rat striatum

日本語

striatum

1998-09-30

Hokkaido University

19p.

短縮題名: D2 up-regulationに対する5-HT系の影響

We examined the modulatory effect of serotonergic activities on haloperidolinduced up-regulation of dopamine D2 receptors in rat striatum. Chronic treatment with haloperidol (0.1, 0.5mg/kg, i.p., 3weeks)increased the number of dopamine D2 receptors, while no increase was observed with atypical antipsychotic drugs clozapine (10mg/kg) and ORG5222 (0.25mg/kg). Chronic treatment with MK212, a nonselective serotonin (5-HT) receptor agonist (2.5mg/kg), or with citalopram, a 5-HT reuptake inhibitor (10mg/kg), potentiated the haloperidol (0.1mg/kg)-induced up-regulation of dopamine D2 receptor, while that with(±)-8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), a 5-HTIA receptor agonist (0.1mg/kg) had no influence on the dopamine D2 receptor up-regulation. Coadministratlon of ritanserin (1mg/kg), a 5-HT2A/2c receptor antagonist, with a low dose of haloperidol (0.1mg/kg), but not with a hlgh dose of the agent (0.5mg/kg) attenuated the dopamine D2 receptor up-regulation. Drug occupation of 5-HT2A and dopamlne D2 receptors in vivo examined using N-ethoxycarbony 1-2-ethoxy-1, 2-dihydro-qunoline (EEDQ) was 69.8% and 45.1%, respectively,after the acute administration of haloperidol (0.1mg/kg) plus ritanserin (1mg/kg). This profile, that 5-HT2A receptors are highiy occupied compared with dopamine D2 receptors, was similar to that of clozapine or ORG 5222. These results suggest that potent 5-HT2A receptor antagonism versus weak dopamine D2 receptor blockade may be involved in the absence of up-regulation of dopamine D2 receptors after chronic treatment with clozapine or ORG 5222.

1998-09-30

乙第5364号

博士(医学)

博士論文

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