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 [H-3]-5-HT (0.1-mu-M, 60 min) or with [H-3]-DA. In hippocampal tissue, the 5-HT uptake blockers chlorimipramine, fluvoxamine, and 6-nitroquipazine (0.1, 1, 10-mu-M) reduced the percentage content of [H-3]-5-HT in a concentration dependent manner. The degree of inhibition of [H-3]-5-HT content produced by the 5-HT uptake inhibitors was not affected by the MAO inhibitors pargyline or amezinium (which by themselves enhanced [H-3] loading) or the catecholamine uptake inhibitor nomifensine (which by itself did not affect [H-3] loading). In caudate nucleus tissue, however, the [H-3]-5-HT accumulation was reduced only at the highest concentration of the 5-HT uptake blockers (10-mu-M). In the additional presence of the MAO inhibitors or nomifensine (which by themselves increased or diminished, respectively, the [H-3] labelling) the 5-HT uptake inhibitors became more potent in reducing the percentage [H-3]-5-HT accumulation of caudate nucleus slices. These results indicate (1) that a false labelling of [H-3]-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 [H-3]-DA, regardless of the presence of pargyline or nomifensine. Tritiated DA and deaminated [H-3]-metabolites were separated in the superfusate of [H-3]-DA-release experiments in caudate nucleus tissue. In the presence of 6-nitroquipazine the percentage efflux of unmetabolized [H-3]-DA was significantly enhanced in a concentration and time dependent manner. In comparison to 6-nitroquipazine, fluvoxamine was less potent in that respect. 6-Nitroquipazine inhibited the electrically evoked [H-3]-DA and [H-3]-ACh release from caudate nucleus slices in a concentration dependent manner. The effects on [H-3]-DA release were abolished in the presence of pargyline. The inhibition of [H-3]-ACh release was significantly diminished by the D2-receptor antagonist domperidone. In conclusion, some 5-HT-related drugs may diminish the release of ACh from caudate nucleus slices via an enhanced dopaminergic transmission due to inhibition of MAO within the dopaminergic terminals.