Presynaptic serotonin receptor-mediated response in mice attenuated by antidepressant drugs and electroconvulsive...

Ligand-binding studies have demonstrated two types of serotonin (5-HT) receptor, 5-HT1 and 5-HT2, in the brains of rodents and there is additional evidence for the existence of 5-HT1 subtypes. Recently a new drug, 8-hydroxy-2-(di-N-propylamino)tetralin (8-OH-DPAT), has been identified which shows high selectivity for binding to 5-HT1 (possibly 5-HT1A) receptors and which binds to presynaptic serotonin autoreceptors in some regions of rat brain. We have shown previously, that this compound produces a hypothermic response in mice, probably via an agonist action at serotonin presynaptic receptors. Here we show that a wide range of antidepressant treatments decrease the hypothermic response to 8-OH-DPAT over a time course comparable to the onset of therapeutic action. Interestingly, repeated electroconvulsive shock (ECS) has the same effect. We propose that this change is relevant to the mechanism of action of antidepressant drugs.