Rapid down-regulation of S2 serotonin receptors by antidepressants: noradrenergic-serotonergic interactions.

Mianserin stereoselectively decreases rat cortical S2 binding, the (+)enantiomer having higher potency. This and other data suggest that an alpha-2 receptor is unlikely to contribute to the mechanism of rapid S2 down-regulation by mianserin. Yohimbine, an alpha-2 antagonist which enhances desipramine-induced S2 decreases, was not dependent on NE or 5-HT release for its effect. Depletion of NE by 75% or 5-HT by 94% did not alter the ability of yohimbine and desipramine to decrease binding. These results raise previously unsuspected mechanisms involved in acute down-regulation of S2 binding by mianserin and yohimbine.