Free and conjugated 3,4-dihydroxyphenylacetic acid and homovanillic acid in brain dopaminergic areas at basal state and after pipotiazine activation.

We have determined free and conjugated 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in discrete brain areas of rats. Conjugated HVA or DOPAC accounted for 22-38% of total acids in striatum, mesolimbic tissue or prefrontal cortex. Activation of dopamine (DA) metabolism by a single injection of pipotiazine palmitic ester (PPZ), a long-lasting neuroleptic, increased free acid levels (DOPAC and HVA) at either dose and conjugate levels after 32 or 50 mg/kg. 48 hours after PPZ-32 mg/kg, the observed increases of conjugates could exceed in some cases those of corresponding free acids. About half of total DOPAC and HVA were conjugated in hypothalamus, PPZ moderately increased free DOPAC (at 32 mg/kg) but did not elevate significantly the conjugated form. It is concluded that sulfation is an important pathway for DOPAC and HVA metabolism in brain and that the determination of both free and conjugated DOPAC or/and HVA may shed additional lights on regional DA metabolism and the effect of drugs thereon.