Effects of Neuromuscular Blocking Agents on Excitatory Transmission and γ-Aminobutyric Acid-A-mediated Inhibition in the Rat Hippocampal Slice

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Abstract

Background

Although neuromuscular blocking agents do not cross the blood-brain barrier, they may penetrate the central nervous system under particular circumstances and eventually cause neurotoxic consequences.

Methods

The effects of neuromuscular blocking agents on excitatory and inhibitory transmission in area CA1 of rat hippocampal slices were investigated using extracellular and intracellular recording techniques.

Results

Application of atracurium in the perfusion medium resulted in a dose-dependent enhancement of excitatory synaptic responses averaging 48.7 +/- 4.3% at a concentration of 10 nM. This effect was correlated with an increase in the size of the presynaptic fiber volley. Laudanosine, but not pancuronium bromide or vecuronium bromide, produced similar changes. In addition, atracurium and laudanosine blocked inhibitory transmission and reduced intracellularly recorded gamma-aminobutyric acidA receptor-mediated potentials. These effects were observed only at concentrations > 1 micro Meter and were not reproduced by pancuronium bromide and vecuronium bromide.

Conclusions

Atracurium and its metabolite, laudanosine, contrary to pancuronium bromide and vecuronium bromide, produce two distinct effects on hippocampal slices. They enhance excitatory transmission and neuronal excitability and they block inhibitory gamma-aminobutyric acid sub A -mediated synaptic responses.

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