THE RELEASE IN VIVO OF DOPAMINE SYNTHESIZED FROM LABELLED PRECURSORS IN THE CAUDATE NUCLEUS OF THE CAT

— To study the release of dopamine (DA) evoked in vivo from the caudate nucleus, a push‐pull cannula was inserted into the head of the caudate nucleus of cats anaesthetised with pentobarbitone sodium (Nembutal), and the tissue in the vicinity of the cannula tip was continuously irrigated with either l ‐[ 14 C]tyrosine or DL‐[ 14 C]3,4‐dihydroxyphenylala‐nine (DOPA). The contents of [ 14 C]DA and of the [ 14 C]acidic metabolites in the perfusates were determined after separation from the labelled precursors by column chromatography, TLC and solvent partition. During perfusion with radioactive tyrosine, only small quantities of [ 14 C]DA appeared in the effluent while the concentrations of the [ 14 C]acidic metabolites gradually increased during the course of the experiment. When [ 14 C]DOPA was substituted for [ 14 C]tyrosine, the proportion of precursor that was converted to DA and released into the effluent as the amine or as its acidic metabolites was increased ten‐fold. In an attempt to increase the resting release of [ 14 C]DA, D‐amphetamine, tropolone or pheniprazine were individually added to the perfusion fluid. Each drug increased the content of [ 14 C]DA in the perfusate, but the enhanced release was maintained only when pheniprazine was added during perfusion with [ 14 C]DOPA. Stimulation of the rostral substantia nigra (A5‐5) and the medial forebrain bundle caused, in a majority of experiments, a two‐to five‐fold increase in the concentration of labelled DA in the effluent. Stimulation of the substantia nigra at A4‐0 did not enhance the release of [ 14 C]DA from the caudate nucleus but did enhance the release from the putamen. Since the increase in the output of [ 14 C]DA was independent of changes in the output of labelled acidic metabolites, the evoked release was apparently not attributable to changes in extracellular fluid dynamics.