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 D-1, D-2 and D-3 receptor were measured in either whole brain or dissected brain regions. D-3 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 D-3 receptor mRNA in nucleus accumbens and olfactory tubercles but not striatum. D-1 and D-2 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 D-1 mRNA in hippocampus and additionally haloperidol and sulpiride down-regulated it in the cerebellum. This work shows that all the drugs tested upregulated D-3 receptor, but effects on D-1 and D-2 receptors were less general. (C) 1998 Elsevier Science Ltd. All rights reserved.