EFFECTS OF NEUROMUSCULAR BLOCKING-AGENTS ON EXCITATORY TRANSMISSION AND GAMMA-AMINOBUTYRIC ACID(A)-MEDIATED INHIBITION IN THE RAT HIPPOCAMPAL SLICE

Background: Although neuromuscular blocking agents do not cross the bl ood-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 techniqu es. Results: Application of atracurium in the perfusion medium resulte d in a dose-dependent enhancement of excitatory synaptic responses ave raging 48.7 +/- 4.3% at a concentration of 10 nM. This effect was corr elated with an increase in the size of the presynaptic fiber volley. L audanosine, but not pancuronium bromide or vecuronium bromide, produce d similar changes. In addition, atracurium and laudanosine blocked inh ibitory transmission and reduced intracellularly recorded gamma-aminob utyric acid(A) receptor-mediated potentials. These effects were observ ed only at concentrations >1 mu M and were not reproduced by pancuroni um bromide and vecuronium bromide. Conclusions: Atracurium and its met abolite, laudanosine, contrary to pancuronium bromide and vecuronium b romide, produce two distinct effects on hippocampal slices. They enhan ce excitatory transmission and neuronal excitability and they block in hibitory gamma-aminobutyric acid(A)-mediated synaptic responses.