Long-Lasting Effects of GABA Infusion Into the Cerebral Cortex of the Rat

[摘要] In electrophysiological terms, experimentalmodels of durable information storage in thebrain include long-term potentiation (LTP),long-term depression, and kindling. Proteinsynthesis correlates with these enduringprocesses. We propose a fourth example oflong-lasting information storage in the brain,which we call the GABA-withdrawal syndrome(GWS). In rats, withdrawal of a chronicintracortical infusion of GABA, a ubiquitousinhibitory neurotransmitter, induced epileptogenesisat the infusion site. This overt GWS lastedfor days. Anisomycin, a protein synthesisinhibitor, prevented the appearance of GWSin vivo. Hippocampal and neocortical slicesshowed a similar post-GABA hyperexcitabilityin vitroand an enhanced susceptibility to LTPinduction. One to four months after the epilepticbehavior disappeared, systemic administrationof a subconvulsant dose of pentylenetetrazolproduced the reappearance of paroxysmalactivity. The long-lasting effects of tonicGABAAreceptor stimulation may be involvedin long-term information storage processes atthe cortical level, whereas the cessation ofGABAAreceptor stimulation may be involvedin chronic pathological conditions, such asepilepsy. Furthermore, we propose that GWSmay represent a common key factor in theaddiction to GABAergic agents (for example,barbiturates, benzodiazepines, and ethanol).GWS represents a novel form of neurono-glialplasticity. The mechanisms of this phenomenonremain to be understood.

[学科分类] 精神健康和精神病学