5-HT3 RECEPTORS WHICH MODULATE [H-3] 5-HT RELEASE IN THE GUINEA-PIG HYPOTHALAMUS ARE NOT AUTORECEPTORS

The 5-HT3 agonist 2-methyl-5-HT had previously been shown to enhance the electrically evoked release of [H-3]5-HT from preloaded slices of the guinea pig brain. In the present study, 2-methyl-5-HT (1 muM) was also found to increase the K+ evoked release of [H-3]5-HT from preloaded slices of the guinea pig hypothalamus and this effect was blocked by the selective 5-HT3 antagonist ondansetron. In the presence of tetrodotoxin, the enhancement of the K+-evoked release of [H-3]5-HT by 2-methyl-5-HT in hypothalamus slices was blocked, thus suggesting that the 5-HT3 receptors mediating this effect are not located directly on 5-HT terminals. In agreement with this, 2-methyl-5-HT did not alter the K+-evoked release of [H-3]5-HT in a synaptosomal preparation of the same brain structure, even at a concentration 10-fold greater than that used in the slices. Taken together, these data indicate that these facilitatory 5-HT3 receptors are not located on 5-HT terminals in the guinea pig hypothalamus and therefore are not autoreceptors. (C) 1993 Wiley-Liss, Inc.