Up-regulation of serotonergic binding sites labeled by [3H]WB4101 following fimbrial transection and 5,7-dihydroxytryptamine-induced lesions.

Lesions of the serotonergic afferents to the hippocampus, by fimbrial transection or by 5,7-dihydroxytryptamine treatment, produce an increase in the Bmax of [3H]WB4101 to its nanomolar affinity binding site, with no effect on its picomolar affinity binding site or on [3H]prazosin binding. The nanomolar site is serotonergic as the serotonergic agonists, serotonin and 8-hydroxydipropylaminotetraline (8-OH-DPAT) have nanomolar affinity for [3H]WB4101 binding when studied in the presence of a prazosin mask (30 nM) of the alpha-1 component of [3H]WB4101 binding. The serotonin receptor antagonists metergoline, lysergic acid diethylamide and lisuride also have high nanomolar affinities while ketanserin, yohimbine, prazosin and noradrenergic agonists have affinities in the micromolar range. Fimbrial transection or 5,7-dihydroxytryptamine injections produced 32% and 44% increases in the Bmax of [3H]WB4101 binding in the presence of a prazosin mask. Serotonin competition for [3H]WB4101 binding was identical in control and experimental tissue from each lesion experiment. Although specific binding of [3H]WB4101 was increased, there was no change in the affinities or the percentages of the two binding components for serotonin competition with [3H]WB4101. These data suggest that removal of the serotonergic input to the hippocampus produces an increase in the Bmax of serotonin receptor binding sites labeled by [3H]WB4101.