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

Chronic treatment (32 days) with sulpiride (100 mg/kg/day) up-regulate d rat brain dopamine D3 receptor mRNA levels by 4-fold but had no effe ct on the mRNA levels encoding the dopamine D1A, D1B or D2 receptors o r the enzymes tyrosine hydroxylase and aromatic amino acid decarboxyla se as measured by multiprobe oligonucleotide solution hybridisation. C lozapine (30 mg/kg/day) increased D3 receptor mRNA levels by 5-fold af ter 4 days, the level dropping to basal after 32 days and also increas ed D1B mRNA levels by 0.5-fold in a similar pattern. Clozapine did not affect any other dopamine receptors or the synthesising enzyme mRNA l evels. We have previously shown that the typical antipsychotics halope ridol and loxapine also increased the mRNA levels of the dopamine D3 r eceptor and these results suggest that up-regulation of dopamine D3 re ceptor mRNA may be associated with the therapeutic action of antipsych otic drugs.