title: Bromocriptine and clozapine regulate dopamine 2 receptor gene expression in the mouse striatum.
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.
authors.affiliation: The Neurosciences Institute, San Diego, CA 92121, USA.
authors.forename: Anthony H
authors.initials: AH
authors.lastname: Stonehouse
authors.forename: Frederick S
authors.initials: FS
authors.lastname: Jones
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001971:Bromocriptine / Q000494:pharmacology*; D003024:Clozapine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D017930:Genes, Reporter; D008297:Male; D051379:Mice; D016716:PC12 Cells; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism*
chemical_list: D000978:Antiparkinson Agents; D014150:Antipsychotic Agents; D018491:Dopamine Agonists; D017448:Receptors, Dopamine D2; D001971:Bromocriptine; D003024:Clozapine