CLOZAPINE AND SULPIRIDE UP-REGULATE DOPAMINE-D(3) RECEPTOR MESSENGER-RNA LEVELS

Chronic treatment (32 days) with sulpiride (100 mg/kg/day) up-regulated rat brain dopamine D3 receptor mRNA levels by 4-fold but had no effect on the mRNA levels encoding the dopamine D1A, D1B or D2 receptors or the enzymes tyrosine hydroxylase and aromatic amino acid decarboxylase as measured by multiprobe oligonucleotide solution hybridisation. Clozapine (30 mg/kg/day) increased D3 receptor mRNA levels by 5-fold after 4 days, the level dropping to basal after 32 days and also increased D1B mRNA levels by 0.5-fold in a similar pattern. Clozapine did not affect any other dopamine receptors or the synthesising enzyme mRNA levels. We have previously shown that the typical antipsychotics haloperidol and loxapine also increased the mRNA levels of the dopamine D3 receptor and these results suggest that up-regulation of dopamine D3 receptor mRNA may be associated with the therapeutic action of antipsychotic drugs.