Fc. Chiodini et al., EFFECTS OF NEUROMUSCULAR BLOCKING-AGENTS ON EXCITATORY TRANSMISSION AND GAMMA-AMINOBUTYRIC ACID(A)-MEDIATED INHIBITION IN THE RAT HIPPOCAMPAL SLICE, Anesthesiology, 88(4), 1998, pp. 1003-1013
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.