Electroconvulsive shock treatments enhance responsiveness of forebrain neurons to serotonin

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.