Release of endogenous amino acids, dopamine, and cyclic AMP from the rat brain: methodological aspects and mutual...

The release from the rat brain of endogenous dopamine, its metabolites, cyclic AMP, transmitter, and other amino acids was studied with push-pull cannula perfusion or dialysis. The amino acid output from the striatum with either perfusion technique was virtually identical. Relative to the tissue content, the egress of the dopamine metabolites and of the non-transmitter (metabolic) amino acids was higher than that of the transmitter substances. The intracellular second messenger cyclic AMP was also released into the perfusate, and its content was enhanced by local application of various biogenic amines. During and after electroconvulsive shocks the release (and presumably the formation) of alanine was enhanced, which may reflect increased glycolysis and transamination in the brain. Following local application of tricyclic antidepressants, the content of transmitter amino acids in push-pull perfusates of the rat thalamus and striatum was enhanced several fold. Such an increase was not found following systemic injection of high doses of mianserin and desmethylimipramine. In contrast, the effect of amphetamine on dopamine release was seen after both local and systemic applications. Locally applied dopamine produced a specific decrease in the release of gamma-aminobutyric acid in both the substantia nigra and in the striatum. Muscimol decreased, whereas picrotoxine enhanced the release of GABA from the rat striatum. Our observations emphasize that transmitter release and brain metabolism can be monitored by perfusion techniques and that the effects of drugs may depend on the route of administration. As has frequently been shown with in vitro techniques, our data indicate the importance of local control of transmitter release in vivo by both autoreceptors and alloreceptors in addition to firing activity.