Perspectives on the Mechanism of Action of Electroconvulsive TherapyAnticonvulsant, Peptidergic, and c‐fosProto‐oncogene Effects
作者:
Takashi Nakajima,
Robert Post,
Agu Pert,
Terrance Ketter,
Susan Weiss,
期刊:
Convulsive Therapy
(OVID Available online 1989)
卷期:
Volume 5,
issue 3
页码: 274-295
ISSN:0749-8055
年代: 1989
出版商: OVID
关键词: Anticonvulsants;Carbamazepine;Electroconvulsive shock;Kindling;Peptides;Proto-oncogene c-fos
数据来源: OVID
摘要:
Although the mechanism of action of electroconvulsive therapy (ECT) in affective illness has remained elusive, it is hoped that the consideration of mechanisms underlying the anticonvulsant efficacy of ECT will provide new insights into its biochemical and neuroanatomical substrates. In the amygdala-kindling model, electroconvulsive seizures (ECS) inhibit both the development and completed phases of kindled seizure evolution, and therefore, ECS is a more potent anticonvulsant modality than carbamazepine, which inhibits only completed kindled seizures. Carbamazepine is increasingly recognized for its acute and prophylactic efficacy in bipolar affective illness. Thus, comparing and contrasting effects of ECS and carbamazepine may provide insights into overlapping mechanisms of anticonvulsant and psychotropic action. Anticonvulsant effects of ECS have been most closely linked to endogenous opiate substances, perhaps acting on delta-opiate receptors, but a wide variety of other neurotransmitter and peptidergic effects are also potential candidates. Electroconvulsive seizures in mice activate the proto-oncogene c-fosin many discrete areas of brain, including a variety of limbic sites, the ventromedial nucleus of the hypothalamus, and the cerebellum. As such, c-fosinduction may provide both an anatomical map of areas potentially activated by ECS and a potential mechanism for initiating a sequence of events that may be important to the mechanism of action of ECT. Although the anticonvulsant effects of ECT may ultimately prove to be separable from those mediating its therapeutic effects in affective illness, seizures and anticonvulsant effects provide easily measurable endpoints for preclinical and clinical studies. Given this clarity of effect, potential anticonvulsant mechanisms can rapidly be identified, enabling direct testing of whether or not these same mechanisms are also critical to the therapeutic effects of ECT in affective illness.
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