A sustained effect of electroconvulsive shock on the turnover of norepinephrine in the central nervous system of the rat.

Electroconvulsive therapy has proved to be the most eff ective form of treatment of depressive illness: extensive clinical experience and a number of controlled studies agree that approximately 80 per cent of depressed patients experience significant, sustained improvement or disappearance of symptoms in the course of a series of electroconvulsive shocks.

Abstract

Although the etiology of the depressive illnesses is unknown, evidence acquired over the past decade has suggested to many authors the hypothesis that these states may result, in part, from a diminished functional activity of norepinephrine in certain regions of the brain. Neurochemical, pharmacological, and behavioral studies have provided a number of findings compatible with this hypothesis. ' Reserpine, a hypotensive and tranquilizing agent which characteristically depletes the brain of norepinephrine and other amines,' has been found in a significant proportion of patients receiving it to result in a state closely resembling endogenous depression. 3 On the other hand, a number of drugs which elevate mood and have been found of value in the treatment of depression appear to act on central norepinephrine in ways which could increase its physiologically active concentration,4 either by inhibiting the enzyme responsible for its presynaptic deamination, by favoring its release, or by inhibiting its re-uptake, presumably at central synapses. Introduced by Cerletti and Bini in 1938,' two decades before modern drug treatments, electroconvulsive therapy has proved to be the most eff ective form of treatment of depressive illness: extensive clinical experience6 and a number of controlled studies7 agree that approximately 80 per cent of depressed patients experience significant, sustained improvement or disappearance of symptoms in the course of a series of electroconvulsive shocks given at intervals of one to a few days. Although there is general agreement on its efficacy, there is little knowledge with which to formulate an explanation of its mechanism of action. Central and peripheral biochemical effects have been observed which are inconstant or attributable to the acute functional disturbances attending the shock itself.8 If a deficiency of norepinephrine were involved in depressive illness, one would expect some change induced by electroconvulsive shock in the availability of this amine in the brain, compatible with one or another of the effects reported for the antidepressant drugs. Rosenblatt and co-workers9 have reported evidence for an increased permeability of the blood: brain barrier to norepinephrine after electroshock, but the elevation in blood norepinephrine which follows such treatment'0 is neither sufficiently great nor prolonged to affect brain concentrations appreciably. Schatalova and Antonov1' have reported no change in brain norepinephrine concentration after a single electrically induced convulsion, but reported a fall after repeated administrations. No effect of electroconvulsive shock has been found on norepinephrine in the brain which could lead to a persistent increase in the physiologically active concentration of that amine in the brain or to a plausible explanation of the sustained clinical improvement which is usually observed.