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

Abstract

Ligand-binding studies have demonstrated two types of serotonin (5-HT) receptor, 5-HT1 and 5-HT2, in the brains of rodents1 and there is additional evidence for the existence of 5-HT1 subtypes2,3. 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) receptors3 and which binds to presynaptic serotonin autoreceptors in some regions of rat brain4,5. We have shown previously, that this compound produces a hypothermie response in mice6,7, probably via an agonist action at serotonin presynaptic receptors. Here we show that a wide range of antidepressant treatments decrease the hypothermie 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.

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