Different effects of serotonin (5-HT) uptake blockers in caudate nucleus and hippocampus of the rabbit: role of monoamine oxidase in dopaminergic terminals.
Slices of rabbit hippocampus or caudate nucleus were incubated with [3H]-5-HT (0.1 microM, 60 min) or with [3H]-DA. In hippocampal tissue, the 5-HT uptake blockers chlorimipramine, fluvoxamine, and 6-nitroquipazine (0.1, 1, 10 microM) reduced the percentage content of [3H]-5-HT in a concentration dependent manner. The degree of inhibition of [3H]-5-HT content produced by the 5-HT uptake inhibitors was not affected by the MAO inhibitors pargyline or amezinium (which by themselves enhanced [3H] loading) or the catecholamine uptake inhibitor nomifensine (which by itself did not affect [3H] loading). In caudate nucleus tissue, however, the [3H]-5-HT accumulation was reduced only at the highest concentration of the 5-HT uptake blockers (10 microM). In the additional presence of the MAO inhibitors or nomifensine (which by themselves increased or diminished, respectively, the [3H] labelling) the 5-HT uptake inhibitors became more potent in reducing the percentage [3H]-5-HT accumulation of caudate nucleus slices. These results indicate (1) that a false labelling of [3H]-5-HT into dopaminergic terminals in the caudate nucleus can be prevented by nomifensine, (2) that the 5-HT uptake blockers seem to accumulate within the dopaminergic terminals, where they may display a MAO inhibitory property. The 5-HT uptake blockers were ineffective on the percentage tritium accumulation of caudate nucleus slices incubated with [3H]-DA, regardless of the presence of pargyline or nomifensine. Tritiated DA and deaminated [3H]-metabolites were separated in the superfusate of [3H]-DA-release experiments in caudate nucleus tissue.(ABSTRACT TRUNCATED AT 250 WORDS)
Lupp
A
A
Neurologische Universitätsklinik, Freiburg, Federal Republic of Germany.
Bär
K I
KI
Lücking
C H
CH
Feuerstein
T J
TJ
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D002421:Caudate Nucleus / Q000187:drug effects* / Q000378:metabolism; D002997:Clomipramine / Q000494:pharmacology; D003864:Depression, Chemical; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D005260:Female; D016666:Fluvoxamine / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009411:Nerve Endings / Q000187:drug effects / Q000378:metabolism*; D009627:Nomifensine / Q000494:pharmacology; D010293:Pargyline / Q000494:pharmacology; D011724:Pyridazines / Q000494:pharmacology; D011814:Quipazine / Q000031:analogs & derivatives / Q000494:pharmacology; D011817:Rabbits; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology
D008996:Monoamine Oxidase Inhibitors; D011724:Pyridazines; D012702:Serotonin Antagonists; D009627:Nomifensine; D012701:Serotonin; D011814:Quipazine; C031227:6-nitroquipazine; D010293:Pargyline; D008995:Monoamine Oxidase; D000109:Acetylcholine; D002997:Clomipramine; D016666:Fluvoxamine; C027784:amezinium; D004298:Dopamine