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

Abstract

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 ofDa (less than 7 fmol/min) and those of the metabolites (approx 0.5 pmol/min). It was calculated that 5% of theDa 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 ofDa and its metabolites, were investigated. The release rate ofDopac correlated well with the drug-induced changes of these metabolites in striatal tissue, however, this was not the case forHva. The increase of striatal levels ofDopac andHva induced by the anaesthesia is a serious limitation of the method. To enable reliable estimation of the release ofDa, 1μM (+)-amphetamine had to be added to the perfusion medium (which may have modified the origin ofDopac andHva in the perfusates). (+)-Amphetamine (5 mg/kg, intravenous) induced a two- to threefold increase in the release ofDa. 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 inDa release, whereas the pronounced and persisting increase inDopac andHva seen after neuroleptics is the result of enhanced metabolism related to increased synthesis ofda.

DOI: 10.1007/BF01961473

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Cite this paper

@article{Radhakishun1983TheRO, title={The release of endogenous dopamine and its metabolites from rat striatum as detected in push-pull perfusates: effects of systemically administered drugs}, author={Fenny S. Radhakishun and Jakob Korf and Kor Venema and B. H. C. Westerink}, journal={Pharmaceutisch Weekblad}, year={1983}, volume={5}, pages={153-158} }