Production of acetylcholine in rat brain following thiamine deprivation and treatment with thiamine antagonists

Abstract— The effects of thiamine deprivation and of treatment with the thiamine antagonists, oxythiamine and pyrithiamine, on the storage and synthesis of acetylcholine were studied in rats. Rats treated with pyrithiamine always developed ataxia and convulsions, and they died in an average of 36 ± 5.0 hr after onset of convulsions. Injections of sublethal doses of eserine after onset of convulsions had no effect or shortened survival time. If injections were started before the onset of convulsions, the survival time was increased to 56 ± 3.3 hr. The content of total acetylcholine-like compounds, measured by bioassay, in the brain was decreased in all three types of thiamine deficiency. On the other hand, the amount of parenterally administered ¹⁴C]pyruvate converted to ¹⁴C]acetylcholine in vivo was affected only by treatment with pyrithiamine. The increase found was probably due to an increased permeability of the blood-brain barrier to the pyruvate. Conversion of ¹⁴C]pyruvate to ¹⁴C]acetylcholine in vitro was decreased significantly in homogenates of brains from both oxythiamine and pyrithiamine-treated animals.