Baclofen-induced encephalopathy in overdose - Modeling of the electroencephalographic effect/concentration relationships and contribution of tolerance in the rat

Progress in Neuro-psychopharmacology & Biological Psychiatry
Magali ChartierLucie Chevillard

Abstract

Baclofen, a γ-amino-butyric acid type-B receptor agonist with exponentially increased use at high-dose to facilitate abstinence in chronic alcoholics, is responsible for increasing poisonings. Baclofen overdose may induce severe encephalopathy and electroencephalographic (EEG) abnormalities. Whether prior prolonged baclofen treatment may influence the severity of baclofen-induced encephalopathy in overdose has not been established. We designed a rat study to characterize baclofen-induced encephalopathy, correlate its severity with plasma concentrations and investigate the contribution of tolerance. Baclofen-induced encephalopathy was assessed using continuous EEG and scored based on a ten-grade scale. Following the administration by gavage of 116 mg/kg baclofen, EEG rapidly and steadily impaired resulting in the successive onset of deepening sleep followed by generalized periodic epileptiform discharges and burst-suppressions. Thereafter, encephalopathy progressively recovered following similar phases in reverse. Periodic triphasic sharp waves, non-convulsive status epilepticus and even isoelectric signals were observed at the most critical stages. Prior repeated baclofen administration resulted in reduced severity (peak: grade...Continue Reading

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Citations

Sep 21, 2018·Frontiers in Psychiatry·Nicolas FranchittoNicolas Simon
May 22, 2020·ACS Chemical Neuroscience·Caitlin N KentCraig W Lindsley

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