Release of endogenous GABA from the rat brain: methodological aspects and the effects of catecholamines

The release of endogenous GABA from the striatum, the substantia nigra and the ventral thalamic nucleus was measured in push-pull canula perfusates with high pressure chromatography and fluorimetric detection. The release of GABA per min is dependent on the flow rates, when low perfusion rates were applied. The GABA release was enhanced by K+ (maximal effect at 50 mM). The effects of various drugs added to the perfusion medium was measured. Imipramine, propranolol and other lipophilic bases (10 microM) enhanced the GABA release in the thalamus. Dopamine (DA), noradrenaline (NA), isoprenaline, clonidine and dibutyryl cyclic AMP decreased the GABA release from the striatum. Haloperidol blocked the effect of DA, but not that of NA. Stimulation of the locus coeruleus decreased GABA output. Destruction of striatal GABA-ergic neurons by kainic acid did not lead to a decreased number of NA-receptors as measured by the formation of cyclic AMP. The results indicate that both catecholamines influence GABA release and that DA and NA act at different receptors. The beta responses are mediated by beta-adrenoceptors that are not confined to striatal GABA neurons.