Ketanserin alters [ 3H]serotonin uptake and release in rat hypothalamus

Ketanserin, a serotonin 2 receptor antagonist, evoked a dose-related non-calcium dependent release of tritium from slices of rat hypothalamus preloaded with [ 3H]serotonin. Concentrations of 1, 5 and 10 μM ketanserin caused a 0.5%, 64% and 110% increase, respectively, in tritium release. Chlorimipramine, a potent inhibitor of the serotonin uptake mechanism, did not alter the spontaneous release of tritium. In addition, 5 μM ketanserin reduced high affinity uptake of 0.1 μM [ 3H]serotonin into rat hypothalamus slices by 36%. These data suggest ketanserin possesses ‘amphetamine-like’ releasing activity and an uptake inhibitory action on serotonin nerve terminals. Both of these properties could mask 5-HT receptor antagonism in vitro and in vivo.