Evidence that [3H]dopamine is taken up and released from nondopaminergic nerve terminals in the rat substantia nigra in vitro.
Potassium chloride (25 mM) and (+)-amphetamine (100 microM) 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 nigrostriatal 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 synaptosomal preparations of striatum, nomifensine but not desipramine 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 nigrostriatal 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 preparations. 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.(ABSTRACT TRUNCATED AT 250 WORDS)
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D002395:Catecholamines / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D003891:Desipramine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology; D006892:Hydroxydopamines; D008474:Medial Forebrain Bundle / Q000502:physiology; D009411:Nerve Endings / Q000378:metabolism*; D009627:Nomifensine / Q000494:pharmacology; D016627:Oxidopamine; D011189:Potassium Chloride / Q000494:pharmacology; D011903:Raphe Nuclei / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism*; D013574:Synaptosomes / Q000378:metabolism
D002395:Catecholamines; D006892:Hydroxydopamines; D005473:Fluoxetine; D009627:Nomifensine; D012701:Serotonin; D011189:Potassium Chloride; D016627:Oxidopamine; D000661:Amphetamine; D003891:Desipramine; D004298:Dopamine