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 3/-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 gamma-aminobutyric acid (GABA). The possible significance of these data to pentobarbital tolerance and dependence development is discussed.
D000818:Animals; D001921:Brain / Q000187:drug effects*; D003513:Cycloheximide / Q000494:pharmacology; D004361:Drug Tolerance; D008239:Lysine / Q000096:biosynthesis; D008297:Male; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D010424:Pentobarbital / Q000494:pharmacology*; D051381:Rats; D013570:Synaptic Membranes / Q000187:drug effects
D009419:Nerve Tissue Proteins; D003513:Cycloheximide; D010424:Pentobarbital; D008239:Lysine