Gamma-aminobutyric acid can both inhibit and facilitate dopamine release in the caudate nucleus of the rabbit.

Slices from rabbit caudate nucleus were preincubated with [3H]dopamine and then superfused and stimulated electrically. gamma-Aminobutyric acid (10-4) and 10(-3) mol/L increased both the basal and the stimulation-evoked overflow of tritium. The effects were not changed by picrotoxin and were only slightly reduced by bicuculline. In the presence of nipecotate 10(-3) mol/L, gamma-aminobutyric acid decreased rather than enhanced the basal and the evoked overflow. The inhibition persisted in the presence of bicuculline. Muscimol did not affect, whereas baclofen decreased, the evoked overflow of tritium. Similar results obtained with synaptosomes that were stimulated by 30 mmol/L K+. The results indicate that gamma-aminobutyric acid can both facilitate and depress the release of dopamine. Facilitation occurs after entry of gamma-aminobutyric acid into the dopaminergic terminal axons, whereas inhibition if probably mediated by a receptor site located in the membrane of these terminals.