Abstract

Electroconvulsive therapy remains one of the most effective treatments of major depression. The effect of electroconvulsive shocks (ECSs) on the responsiveness of hippocampal pyramidal neurons to serotonin, norepinephrine, gamma-aminobutyric acid and 5-methoxydimethyltryptamine was studied in rats pretreated with one or six ECSs. Control rats were given subconvulsive shocks. Microiontophoretic experiments were conducted 36 hr after the last shock in urethane-anesthetized or low cerveau isolé preparations. Responsiveness of hippocampal pyramidal neurons to microiontophoretic applications of serotonin was markedly enhanced in rats pretreated with six ECSs. Responsiveness to 5-methoxydimethyltryptamine, a postsynaptic agonist which is not an adequate substrate for the high-affinity serotonin reuptake process, was also enhanced in rats pretreated with six ECSs, indicating that the increased responsiveness to serotonin was due to a postsynaptic modification. The effects of norepinephrine and of gamma-aminobutyric acid applied on the same neurons were not modified by repeated ECS pretreatment. A single ECS failed to modify responsiveness to either serotonin or 5-methoxydimethyltryptamine. Inasmuch as long-term tricyclic antidepressant drug administration has been shown to produce a similar sensitization to serotonin, the present results suggest that enhancement of serotonergic neurotransmission might mediate the therapeutic effect of both types of treatment in major depression.