Evaluation of the role of pre- and postsynaptic serotonergic receptors in electroconvulsive shock therapy.

Despite the well-established clinical efficacy of electroconvulsive therapy (ECT) in the treatment of affective disorders, there is no generally accepted theory regarding its mode of action. Pre- and postsynaptic serotonin (5-hydroxytryptamine, 5-HT) receptors were studied following treatment of rabbits with electroconvulsive therapy (8 shocks). No change was observed in the binding at the postsynaptic 5-HT2 receptor in frontoparietal cortex, as indicated by an unchanged affinity and by the total number of receptors. In control rabbits, exogenously added serotonin and metitepin modulated the electrically evoked 3H-serotonin release, probably by acting on a presynaptic serotonin autoreceptor. Following electroconvulsive therapy, exogenous serotonin still inhibited the 3H-serotonin release, whereas metitepin had lost its enhancing effect. This observation provides evidence for a decreased amount of endogenous neurotransmitter present in the synaptic cleft at stimulation. The results indicate that postsynaptic receptor changes following antidepressant treatments are related to the presynaptic autoreceptor changes.