The release of endogenous dopamine and its metabolites from rat striatum as detected in push-pull perfusates: effects of systemically administered drugs
- 18 Downloads
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.
KeywordsDopamine Haloperidol Amphetamine High Pressure Liquid Chromatography Apomorphine
Unable to display preview. Download preview PDF.
- Glowinski, J., A. Cheramy andM.F. Giorguieff (1979) In:The Neurobiology of Dopamine (Horn, A.S., J. Korf andB.H.C. Westerink, Eds.) Academic Press, London, 199–216.Google Scholar
- Imperato, A., andG. di Chiara (1982)Neurosci. Lett., Suppl. 10, S249.Google Scholar
- König, J.F.R., andR.A. Klippel (1963) In:The Rat Brain. Forebrain and Lower Parts of the Brain Stem. R.E. Krieger Publishing Co. Inc., New York, 162.Google Scholar
- Ungerstedt, U., M.Herrera-Marschitz, U.Jungnelius, L.Stahle, U.Tossman and T.Zetterström (1981) Symposium on Dopamine, Osaka, 219–231.Google Scholar