Kumatoshi Ishihara and Masashi Sasa
Department of Pharmacology, Hiroshima University School of Medicine,
1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan
Abstract: Electroconvulsive therapy (ECT) is used to treat drug-resistant
depressive disorders. The results of studies on the mechanism underlying
the effectiveness of ECT on depression are still controversial. ECT stimulus
is usually larger than the threshold of induction of seizures and activation
of whole-brain is believed to be necessary to produce therapeutic effects.
A single ECT session induces alterations of the electroencephalogram (EEG)
including initial epileptic discharges, then slow waves, and finally flattened
EEG. Repeated ECT results in an increasing number of slower waves in the
EEG for as long as a month. ECT-induced changes in various neurotransmitter
systems have also been reported. Serotonin (5-hydroxytryptamine, 5-HT) is
one of the most important neurotransmitters involved in depressive illness,
and ECT alters several 5-HT-receptor subtypes in the central nervous system.
5-HT1A receptors in post-synaptic neurons are sensitized by repeated
ECT, but those in pre-synaptic neurons (auto-receptors) are not changed.
In addition, our electrophysiological studies have shown that ECT increases
sensitivity to 5-HT of 5-HT3 receptors in the hippocampus, resulting
in an increase in release of neurotransmitters such as glutamate and gamma-aminobutyric
acid. In contrast, ECT decreases the auto-receptor functions in noradrenergic
and dopaminergic neurons in the locus coeruleus and substantia nigra, respectively,
resulting in an increase in release of noradrenaline and dopamine. In conclusion,
5-HT1A-receptor sensitization may be important for explaining
the effectiveness of ECT, as this change induces a decrease in the number
of 5-HT2A receptors that are elevated in depressive patients.
Facilitation of neurotransmitter releases due to 5-HT3-receptor
sensitization by ECT may also play an important role in effective treatment
of depressive patients refractory to therapeutic drugs.
Keywords: Electroconvulsive therapy (ECT), Serotonin receptor, Depressive
disorder