Stimulation of dopamine release by GABA in rat striatal slices

Abstract

The effect of GABA on the release of dopamine (DA) from dopaminergic terminals was examined in striatal slices of the rat. The slices were continuously superfused with L-[ 3H]tyrosine and [ 3H]DA released was estimated in serial 2.5 min superfusate fractions. GABA from 10 −5 M to 10 −3 M stimulated the spontaneous release of [ 3H]DA. The intensity of the effect appeared to be concentration dependent. The GABA stimulatory effect on [ 3H]DA release persisted during the entire application of GABA for periods as long as 50 min. At a much higher concentration (10 −1 M) GABA inhibited the spontaneous release of [ 3H]DA. At a concentration (10 −4 M) which stimulated [ 3H]DA release, GABA had no effect on [ 3H]DA uptake or [ 3H]tyrosine initial transport in striatal sucrose homogenates. Furthermore it did not affect DA synthesis as indicated by the estimation of the conversion index of tyrosine into DOPA ( 3H 2O formed from L-[3,5- 3H]tyrosine/tyrosine specific activity in tissues). The stimulatory effect of GABA (5 × 10 −5 M) on the spontaneous release of [ 3H]DA was not detectable when slices were superfused in the absence of calcium or in the presence of tetrodotoxin (5 × 10 −7 M). It was markedly reduced in the presence of picrotoxin (10 −5 M), a GABA antagonist. Finally, like GABA, GABA agonists such as muscimol and compounds structurally related to GABA such as lioresaal and gammahydroxybutyrate stimulated [ 3H]DA spontaneous release. Gamma-hydroxylioresal, an inactive metabolite of lioresal, was without effect. These various results suggest that GABA stimulates specifically the release of DA endogenously synthesized in dopaminergic terminals. The blockade of the GABA stimulatory effect by tetrodotoxin (5 × 10 −7 M) suggests that the GABA receptors mediating the action of GABA are not located presynaptically on dopaminergic terminals but on neurons or neuronal afferences within the striatum.