The release of endogenous dopamine and its metabolites from rat striatum as detected in push-pull perfusates: effects of systematically administered drugs.

The release of dopamine (DA) and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) was determined in push-pull perfusates from the striatum of the anaesthetized rat with high pressure liquid chromatography and electrochemical detection. Striking differences were found between the released amounts of DA (less than 7 fmol/min) and those of the metabolites (approx 0.5 pmol/min). It was calculated that 5% of the DA metabolites left the striatum via the push-pull cannula. The effects of systemic application of apomorphine, (+)-amphetamine, haloperidol or haloperidol in combination with amfonelic acid on the release of DA and its metabolites, were investigated. The release rate of DOPAC correlated well with the drug-induced changes of these metabolites in striatal tissue, however, this was not the case for HVA. The increase of striatal levels of DOPAC and HVA induced by the anaesthesia is a serious limitation of the method. To enable reliable estimation of the release of DA, 1 microM (+)-amphetamine had to be added to the perfusion medium (which may have modified the origin of DOPAC and HVA in the perfusates). (+)-Amphetamine (5 mg/kg, intravenous) induced a two- to threefold increase in the release of DA. Systemic administration of apomorphine, haloperidol or haloperidol in combination with amfonelic acid did not change the output of the neurotransmitter in the push-pull cannula. This implies that neuroleptics cause only a small and transient rise in DA release, whereas the pronounced and persisting increase in DOPAC and HVA seen after neuroleptics is the result of enhanced metabolism related to increased synthesis of DA.