Evidence for autoreceptor modulation of endogenous dopamine release from rabbit caudate nucleus in vitro

This study was designed to determine if the release of endogenous dopamine (DA), like [3H]DA, is modulated by inhibitory autoreceptors. A high-performance liquid chromatographic assay was developed which was capable of detecting the basal efflux and electrically evoked overflow of endogenous DA and dihydroxyphenylacetic acid (DOPAC), the primary DA metabolite. In the absence of neuronal uptake inhibitors the stimulation-evoked overflow of endogenous DA was entirely in the form of DOPAC, whereas overflow consisted primarily of DA in the presence of uptake inhibition. The evoked overflow of DA and DOPAC was abolished by reduction of the Ca++ concentration of the superfusion medium from 1.3 to 0.13 mM. The DA receptor antagonist sulpiride (1 microM) increased DOPAC overflow by 41%. Nomifensine (10 microM) increased slightly and cocaine (10 microM) decreased slightly the total overflow of endogenous compounds (DA plus DOPAC). Combination of nomifensine and sulpiride or cocaine and sulpiride increased total overflow of endogenous compounds by 217 and 120%, respectively, as compared to the neuronal uptake inhibitors alone. The DA receptor agonists apomorphine (0.3 microM) and bromocriptine (1 microM) inhibited DOPAC overflow by 92 and 83%, respectively. However, apomorphine and bromocriptine failed to inhibit endogenous DA release in the presence of nomifensine. Sulpiride antagonized the inhibitory effects of both apomorphine and bromocriptine. In experiments in which [3H]DA and endogenous DA overflow were measured simultaneously, radiolabeled DA behaved exactly like the endogenous transmitter.(ABSTRACT TRUNCATED AT 250 WORDS)