On the possible role of brain protein synthesis in functional barbiturate tolerance

Robert J. Hitzemann, Horace H. Loh

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9 Scopus citations


Pentobarbital pellet implantation increased more than 200% the ED50 dose of pentobarbital required to induce loss of the righting reflex within 2 min of i.p. injection and increased the onset of barbital-induced sleep. Both tests of functional barbiturate tolerance were blocked by the intraventricular injection of cycloheximide. The effects of acute (45 mg/kg i.p.) and chronic (pellet implantation) pentobarbital treatment on the incorporation of 3H-lysine into the protein of various subcellular fractions of the cortex and subcortex were studied. In the subcortex, chronic pentobarbital treatment significantly stimulated protein synthesis 40-50% in the microsomal, soluble and mitochondrial fractions. Both acute and chronic pentobarbital treatments significantly increased (3H-lys)-protein accumulation in a fraction of synaptic plasma membranes derived from a population of nerve ending particles (NEP) enriched in γ-aminobutyric acid (GABA). The possible significance of these data to pentobarbital tolerance and dependence development is discussed.

Original languageEnglish (US)
Pages (from-to)163-173
Number of pages11
JournalEuropean Journal of Pharmacology
Issue number1
StatePublished - Nov 1976

Bibliographical note

Funding Information:
of this manuscript. The authors also wish to thank Barbara Hitzemann for her technical assistance. The comments and suggestions of Drs. I.K. Ho and V.C. Sutherland during the course of the study are also gratefully acknowledged. This study was supported in part by NIMH grant DA-00564.

Copyright 2014 Elsevier B.V., All rights reserved.


  • Cycloheximide
  • Pentobarbital
  • Protein synthesis
  • Synaptic plasma membrane
  • Tolerance


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