Antipsychotic regulation of dopamine D1, D2 and D3 receptor mRNA.
A range of antipsychotic drugs, both "typical" and "atypical", was administered to rats over a time course and at several different dosages. The mRNA levels of dopamine D1, D2 and D3 receptor were measured in either whole brain or dissected brain regions. D3 receptor mRNA was up-regulated in whole brain by clozapine (10 and 30 but not 3 mg/kg/day), sulpiride (50 and 100 but not 20 mg/kg/day). haloperidol (3 but not 1 or 0.3 mg/kg/day), flupenthixol (3 but not 1 or 0.3 mg/kg/day), pimozide (4.5 but not 1.5 or 0.5 mg/kg/day) and loxapine (1.2 and 4 mg/kg/day but not 0.4 mg/kg/day). Sulpiride (100 mg/kg/day), clozapine (30 mg/kg/ day) and haloperidol (3 mg/kg/day) all up-regulated the D3 receptor mRNA in nucleus accumbens and olfactory tubercles but not striatum. D1 and D2 receptor mRNA was up-regulated in whole brain by haloperidol and loxapine only, and in the case of haloperidol this was localized to striatum and prefrontal cortex. Haloperidol, clozapine and sulpiride all down-regulated D1 mRNA in hippocampus and additionally haloperidol and sulpiride down-regulated it in the cerebellum. This work shows that all the drugs tested up-regulated D3 receptor, but effects on D1 and D2 receptors were less general.
D'Souza
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U
Department of Psychological Medicine, University of Wales College of Medicine, Cardiff, UK.
McGuffin
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P
Buckland
P R
PR
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D003024:Clozapine / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009693:Nucleic Acid Hybridization; D015345:Oligonucleotide Probes; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000096:biosynthesis*; D017448:Receptors, Dopamine D2 / Q000096:biosynthesis*; D050637:Receptors, Dopamine D3; D013469:Sulpiride / Q000494:pharmacology
D014150:Antipsychotic Agents; C493595:Drd3 protein, rat; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013469:Sulpiride; D003024:Clozapine; D006220:Haloperidol