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Pharmaceutisch Weekblad

, Volume 5, Issue 4, pp 153–158 | Cite as

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

  • F. S. Radhakishun
  • J. Korf
  • K. Venema
  • B. H. C. Westerink
Original Articles

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.

Keywords

Dopamine Haloperidol Amphetamine High Pressure Liquid Chromatography Apomorphine 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Royal Dutch Association for Advancement of Pharmacy 1983

Authors and Affiliations

  • F. S. Radhakishun
    • 1
  • J. Korf
    • 2
  • K. Venema
    • 2
  • B. H. C. Westerink
    • 1
  1. 1.Department of Medicinal ChemistryLaboratory of Pharmaceutical and Analytical ChemistryAW GroningenThe Netherlands
  2. 2.Department of Biological PsychiatryUniversity of GroningenEZ GroningenThe Netherlands

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