Bromocriptine and clozapine regulate dopamine 2 receptor gene expression in the mouse striatum.
J Mol Neurosci
; 25(1): 29-36, 2005.
Article
em En
| MEDLINE
| ID: mdl-15781964
ABSTRACT
In a previous study, we showed that the psychoactive drug caffeine alters the expression of the dopamine 2 receptor (D2R) gene in vitro and in vivo. Here, we report that acute administration of antipsychotic and anti-parkinsonian drugs also regulate D2R gene expression in PC12 cells and in the mouse striatum. Treatment of PC12 cells with the atypical antipsychotic and specific 5-HT antagonist clozapine (60 microM) reduced D2R/luciferase reporter expression by 46% after 24 h. However, male and female mice treated with a clinical dose of clozapine (10 mg/kg) showed no changes in striatal D2R mRNA expression when assayed by quantitative RT-PCR. Treatment of PC12 cells with the specific D2R agonist anti-parkinsonian drug, bromocriptine mesylate (BCM; 5 microM) also resulted in decreased D2R/luciferase reporter activity (27%). In contrast to clozapine, a clinical dose of BCM (16 mg/kg) led to a 21% decrease and a 45% increase in striatal D2R mRNA expression in male and female mice, respectively, after 24 h. Coadministration of clozapine and BCM in PC12 cells resulted in a synergistic decrease in D2R/luciferase reporter expression (68%), and coadministration of these drugs in vivo led to decreases in striatal D2R mRNA expression in both male and female mice (45% and 22%, respectively). Collectively, these results indicate that clozapine, BCM, or a combination of these drugs have differential effects on dopamine receptor gene expression and might also affect striatal physiology in a sexually dimorphic manner.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antipsicóticos
/
Bromocriptina
/
Regulação da Expressão Gênica
/
Clozapina
/
Receptores de Dopamina D2
/
Agonistas de Dopamina
/
Corpo Estriado
Limite:
Animals
Idioma:
En
Ano de publicação:
2005
Tipo de documento:
Article