Electroconvulsive Seizures Inhibit Amygdala Kindling: Implications for Mechanisms of Action in Affective Illness

Abstract

Amygdala kindling, the progressive development of seizures following repeated electrical stimulation, has been used as a model of epileptogenesis, neural memory, and the development of behavioral alterations. In an attempt to interfere with the kindling process, electroconvulsive seizures (ECS) were administered 6 h prior to or immediately after once-daily amygdala stimulation. ECS compared with sham ECS 6 h prior to kindling profoundly inhibited the development of amygdala-kindled seizures, while ECS immediately after the afterdischarge (AD) were not effective. In a second study, seven daily ECS, but not a single ECS followed by a 6-day delay, markedly suppressed established amygdala-kindled seizures compared with sham ECS controls. The generalized seizures of ECS thus appear to be paradoxically anticonvulsant to limbic seizures. Carbamazepine, a potent anticonvulsant for temporal lobe and limbic seizures in animals and man, inhibits amygdala-kindled seizures and is effective in the treatment of manic-depressive illness. The current findings suggest the possibility that the efficacy of ECS in affective illness may be, in part, related to its limbic antikindling and anticonvulsant effects.

Repeated ECS and fluoxetine administration have equivalent effects on hippocampal synaptic plasticity

“…It is unlikely that a kindling phenomenon can account for the results seen with repeated ECS since spontaneous behavioural seizures were not observed and there were no localised seizures during electrophysiological recording. There is no evidence to suggest that ECT produces kindling in human brain (Small et al 1981) and furthermore, repeated ECS inhibits the development of kindling in animals (Post et al 1984).…”

Depression in Epilepsy: A Common but Often Unrecognized Comorbid Malady

“…Blackwood et al found that the incidence of seizures in patients following treatment with ECT was no higher than in the general population (131). In fact, several studies have shown that ECT increases seizure threshold by 50 to 100% (130,(133)(134)(135)(136). If patients are taking lithium at the time ECT is being considered, some authors have suggested that it be discontinued at least 5 days prior to ECT because of the risk of prolonged seizures, memory loss, and confusion (137).…”

Topiramate Normalizes Hippocampal NPY-LI in Flinders Sensitive Line ‘Depressed’ Rats and Upregulates NPY, Galanin, and CRH-LI in the Hypothalamus: Implications for Mood-Stabilizing and Weight Loss-Inducing Effects

“…ECS also increase NPY-LI in the hippocampus of FSL and normal rats (Jiménez Vasquez et al, 2000;Husum et al, 2000;Mathé et al, 1998;Stenfors et al, 1989). ECT has pronounced mood-normalizing and antipsychotic properties, but is also an anticonvulsant, as shown both in patients and in animal models of epilepsy (Nakajima et al, 2001;Post et al, 1984). Based on findings of increased hippocampal NPY release following kainic acid and ECS-induced seizures (Husum et al, 2000(Husum et al, , 1998, attenuating effects of exogenous NPY against pharmacologically induced seizures (Woldbye, 1998;Woldbye et al, 1997Woldbye et al, , 1996, increased or even fatal vulnerability of NPY knock-down and knock-out mice to seizures (DePrato Primeaux et al, 2000;Baraban et al, 1997;Erickson et al, 1996), and altered brain synthesis of NPY in seizure-prone animals (Jinde et al, 1999;Amano et al, 1996;Sadamatsu et al, 1995), NPY has been suggested to act as an endogenous anticonvulsant (Bolwig et al, 1999).…”