Interaction between 5-HT uptake inhibition and activation of 5-HT autoreceptors by exogenous agonists in rat cerebral...

Rat cerebral cortex slices or synaptosomes were labelled with 3H-5-hydroxytryptamine (3H-5-HT) and subsequently superfused. They were depolarized by electrical stimulation (slices) or with high K+ (slices and synaptosomes). Continuous electrical stimulation (2 Hz, 24 mA, 2 ms) and continuous or discontinuous K+ depolarization (15-25 mM) were used. 1. Continuous electrical stimulation or continuous K+-depolarization of slices evoked a steady overflow of tritium that slowly decayed with time. 2. Exposure to increasing concentrations of 5-methoxy-3(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole succinate (RU 24969) (0.001-0.1 microM) during continuous electrical stimulation produced a concentration-dependent decrease in tritium overflow. Citalopram (1 microM) counteracted the effect of RU 24969. 3. RU 24969 inhibited the evoked 3H-overflow and citalopram reduced the effect of RU 24969 also during continuous depolarization of slices with 20 mM K+. Similar results were obtained by using 5-methoxytryptamine or LSD. 4. In slices 1 microM citalopram increased significantly the tritium overflow evoked by electrical stimulation or by 20 mM K+-depolarization. 5. Increasing the K+ concentration from 20 mM to 25 mM mimicked the effects of 1 microM citalopram both on the RU 24969 activity and on the evoked tritium overflow. 6. RU 24969 (0.001-0.1 microM) decreased in a concentration-dependent way the release of tritium from cortical synaptosomes depolarized with K+ (15-20 mM). The presence of 1 microM citalopram did not modify significantly the effect of the agonist. Citalopram was ineffective also when the serotonin uptake carrier in superfused synaptosomes was activated by tryptamine.(ABSTRACT TRUNCATED AT 250 WORDS)