Biphasic and Opposite Effects of Dopamine and Apomorphine on Endogenous GABA Release in the Rat Substantia Nigra

Abstract: A push-pull cannula technique was used to study the in vivo release of endogenous GABA in the rat substantia nigra. Intranigral application of both dopamine (DA) and apomorphine produced biphasic changes in the rate of endogenous GABA release. The presence of 10 μM-DA in the perfusion medium increased GABA release (140%). At 25 μM-DA, both stimulation and inhibition of the nigral GABA release were observed. Higher concentrations of DA produced a decrease of the GABA release (50%). A small amount of apomorphine (10 μM in the perfusion medium) resulted in a decrease in GABA release (75%). Application of 25 μM-apomorphine produces opposite effects, similar to those observed after addition of 25 μM-DA. We observed an enhanced GABA release from the substantia nigra at 100 μM-apomorphine in the perfusion medium (360%). The presence of 5 μM-haloperidol produced a small decrease in the rate of GABA release (80%). Both the inhibitory effect of 25 μM-DA and the excitatory effect of 100 μM-apomorphine could be blocked by haloperidol added to the perfusion medium. Dibutyryl cyclic AMP (1.5 mM) and 2-amino-6, 7-dihydroxyl(1, 2, 3, 4) tetrahydronapthalene (ADTN) (50 μM) added to the perfusion medium produced an inhibition of nigral GABA release (55% and 35% respectively) similar to that observed after addition of 50 μM-DA. The amounts of lysine and ethanolamine (measured with GABA concurrently) released into the perfusion medium did not change in most of the experiments. The changes in the rates of release of these compounds that were observed in some experiments were either in the same or in the opposite direction of the change in GABA release. These results suggest that dopaminergic processes within the substantia nigra affect GABA-ergic neurotransmission and that DA and apomorphine have different effects on GABA release.