Elsevier

Brain Research

Volume 209, Issue 1, 23 March 1981, Pages 177-188
Brain Research

Barbiturate enhancement of GABA-mediated inhibition and activation of chloride ion conductance: correlation with anticonvulsant and anesthetic actions

https://doi.org/10.1016/0006-8993(81)91179-3Get rights and content

Summary

The anesthetic-sedative barbiturate pentobarbital (PB) and the anticonvulsant barbiturate phenobarbital (PhB) were applied to mammalian spinal cord neurons in primary dissociated cell culture to assess their effects on: (1) postsynaptic GABA-responses; (2) paroxysmal activity produced by the convulsant bicuculline; (3) resting membrane properties; and (4) spontaneous neuronal activity. The results demonstrated that: (1) anticonvulsant actions occured at barbiturate concentrations which augmented GABA-responses; (2) anesthetic actions occurred at barbiturate concentrations which produced direct increases in chloride conductance; (3) both anticonvulsant and anesthetic actions occurred at clinically relevant concentrations; and (4) concentrations of PhB, but not PB, which produced GABA-augmentation and direct conductance changes were widely separated. These findings support the hypotheses that augmentation of GABA-mediated inhibition and possibly reduction of glutamate (GLU)-mediated excitation form the basis at least in part for barbiturate anticonvulsant action and that addition of direct increases in chloride conductance to augmentation of GABA-mediated inhibition and reduction of GLU-mediated excitation may partially underlie anesthetic-sedative barbiturate action.

References (31)

  • BlausteinM.P. et al.

    Barbiturate inhibition of calcium uptake by depolarized nerve terminals in vitro

    Molec. Pharmacol.

    (1975)
  • CohenP.J. et al.

    Signs and stages of anesthesia

  • CutlerR.W.P. et al.

    Effect of barbiturates on release of endogenous amino acids from rat cortex slices

    Neurochem. Res.

    (1979)
  • KalantH. et al.

    Effects of ethanol and pentobarbital on release of acetylcholine from cerebral cortex slices

    J. Pharmacol. exp. Ther.

    (1967)
  • LeppikI.E. et al.

    Intravenous phenytoin and phenobarbital; anticonvulsant action, brain content, and plasma binding in rat

    Epilepsia (Amst.)

    (1979)
  • Cited by (0)

    View full text