Evidence that [3H]Dopamine Is Taken Up and Released from Nondopaminergic Nerve Terminals in the Rat Substantia Nigra In Vitro

Abstract

Potassium chloride (25 mM) and (+)-amphet-amine (100 μM) both stimulated the release of radioactivity from slices of substantia nigra preincubated with [³H]3,4-dihydroxyphenylethylamine ([³H]dopamine). Potassium chloride (25 mM) released radioactivity from slices of both zona compacta and zona reticulata. Prior 6-hydroxydopamine (6-OHDA) lesions of one nigro-striatal pathway did not reduce the spontaneous release of radioactivity, or the potassium chloride- or amphetamine-induced release of radioactivity from slices of nigra ipsilateral to the lesion after preincubation with [³H]dopamine. The accumulation of radioactivity following incubation of nigral slices from 6-OHDA-lesioned animals with [³H]dopamine was increased when compared to uptake into slices from intact tissue. In synap-tosomal preparations of striatum, nomifensine but not de-sipramine or fluoxetine inhibited [³H]dopamine uptake. In contrast, nomifensine, desipramine, and fluoxetine all inhibited [³H]dopamine uptake in nigral synaptosomal preparations. Following 6-OHDA lesions of one nigro-striatal pathway the uptake of [³H]dopamine into nigral synaptosomal preparations was unchanged but uptake into striatal preparations was substantially decreased. In contrast, bilateral electrolesions of the dorsal and medial raphe nuclei reduced [³H]dopamine uptake into nigral preparations but not into striatal synaptosomes. The uptake of [³H]5-hydroxytryptamine ([³H]5-HT) into synaptosomal preparations of substantia nigra was abolished by fluoxetine and reduced by desipramine, but was unaffected by nomifensine. In contrast, fluoxetine, desipramine, and nomifensine all inhibited [³H]5-HT uptake into striatal synaptosomal reparations. Following 6-OHDA lesions of one nigro-striatal pathway the uptake of [³H]5-HT into nigral synaptosomal preparations was unchanged but uptake into striatal preparations was reduced. In contrast, bilateral electrolesions of the dorsal and medial raphe nuclei reduced [³H]5-HT uptake into both nigral and striatal synaptosomal preparations. These results suggest that in tissue preparations from substantia nigra, the in vitro uptake and release of [³H]dopamine may not reflect dendritic dopamine function alone, but may involve other neuronal processes, particularly 5-HT neurones.