FEEDBACK STIMULATION OF SOMATODENDRITIC SEROTONIN RELEASE - A 5-HT3 RECEPTOR-MEDIATED EFFECT IN THE RAPHE NUCLEI OF THE RAT

Slices from rat midbrain containing the raphe nuclei and from hippocam pus were prepared, loaded with [H-3]5-HT and superfused and the restin g and the electrically stimulated [H-3]5-HT release was measured, The 5-HT3 receptor agonist 2-methyl-5-HT (1 to 10 mu mol/l) increased the resting tritium outflow in superfused raphe nuclei slices, EC50 5.3 mu mol/l. The 2-methyl-5-HT-induced increase of tritium outflow was an e xternal Ca2+-independent process and was not altered by reserpine pret reatment but it was reversed by addition of the 5-HT uptake inhibitor fluoxetine (1 mu mol/l). The 5-HT3 receptor antagonists ondansetron an d GYKI-46 903 (1 mu mol/l) did not antagonize the stimulatory effect o f 2-methyl-5-HT on resting tritium outflow, 2-Methyl-5-HT in lower con centration increased the electrically induced tritium overflow from ra phe nuclei slices (EC50 0.56 mu mol/l) and also from hippocampal slice s preloaded with [H-3]5-HT. These effects were reversed by 1 mu mol/l of ondansetron and GYKI-46903. The 5-HT3 receptor antagonists (1 mu mo l/l) were without effects on depolarization-evoked [H-3]5-HT release a t 2 Hz stimulation, when 10 Hz stimulation was used, ondansetron and G YKI-46 903 reduced the tritium overflow from raphe nuclei slices, Thes e data indicate that 5-HT3 receptors positively alter depolarization-i nduced somatodendritic 5-HT release in the raphe nuclei, They also sho w that 2-methyl-5-HT is able to evoke 5-HT release not only from vesic les but also from cytoplasmic stores via a transporter-dependent excha nge process. (C) 1998 Elsevier Science Inc.