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

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.