Differential effects of subchronic treatments with atypical antipsychotic drugs on dopamine D2 and serotonin 5-HT2A receptors in the rat brain.
The effects of 3-week treatment with a typical antipsychotic drug chlorpromazine and three atypical antipsychotic drugs (risperidone, olanzapine and perospirone) on the binding to dopamine D2 and serotonin 5-HT2A receptors were examined in the rat stratum and frontal cortex, respectively. Subchronic treatment with chlorpromazine (10 mg/kg) and perospirone (1 mg/kg) significantly increased 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-HT2A 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 D2 and 5-HT2A receptors using N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) suggested that high occupation of 5-HT2A receptors with lower D2 receptor occupancy might be involved in the absence of up-regulation of D2 receptors after subchronic treatment with some atypical antipsychotic drugs.
Kusumi
I
I
Department of Psychiatry, Hokkaido University School of Medicine, Sapporo, Japan. ikusumi@med.hokudai.ac.jp
Takahashi
Y
Y
Suzuki
K
K
Kameda
K
K
Koyama
T
T
D000818:Animals; D014150:Antipsychotic Agents / Q000378:metabolism / Q000494:pharmacology*; D001569:Benzodiazepines; D001923:Brain Chemistry / Q000187:drug effects*; D002746:Chlorpromazine / Q000378:metabolism / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007211:Indoles / Q000378:metabolism / Q000494:pharmacology; D054833:Isoindoles; D008297:Male; D000077152:Olanzapine; D010890:Pirenzepine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D011804:Quinolines / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044402:Receptor, Serotonin, 5-HT2A; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism*; D018967:Risperidone / Q000378:metabolism / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000378:metabolism / Q000494:pharmacology; D013844:Thiazoles / Q000378:metabolism / Q000494:pharmacology
D014150:Antipsychotic Agents; D001569:Benzodiazepines; D002746:Chlorpromazine; D018492:Dopamine Antagonists; D007211:Indoles; D054833:Isoindoles; D000077152:Olanzapine; D010890:Pirenzepine; D011804:Quinolines; D044402:Receptor, Serotonin, 5-HT2A; D017448:Receptors, Dopamine D2; D011985:Receptors, Serotonin; D018967:Risperidone; D017367:Selective Serotonin Reuptake Inhibitors; D013844:Thiazoles; C000470:EEDQ; C065533:perospirone