title: Effects of diazepam on blood choline and acetylcholine turnover in brain of mice.
abstract: The effect of diazepam on the acetylcholine (ACh) synthesizing system has been studied in mouse brain in vivo. ACh and choline (Ch) were analyzed by gas chromatography - mass spectrometry using deuterated internal standards. Turnover of ACh was studied by following the incorporation of Ch into ACh after an intravenous injection of [2H6]-Ch. The mice were killed by focussed microwave irradiation on the head. Diazepam was found to increase the endogenous level of Ch, while the concentration of [2H6]-Ch was only half of that of the controls. The incorporation of [2H6]-Ch into [2H6]-ACh was decreased, while the endogenous level of ACh was slightly increased. The turnover rate of ACh was decreased, consistent with a decrease in neuronal excitability induced by diazepam. The elevated endogenous Ch-level and the lower concentration of [2H6]-Ch in the brain, might be explained by an effect of diazepam on the Ch-transport across the blood-brain barrier. This theory is supported by experiments where levels of endogenous and [2H6]-labelled Ch were analyzed in blood following an intravenous injection of [2H6]-Ch. The [2H6]-Ch was found to be eliminated faster in blood from diazepam treated mice. The increased blood level of endogenous Ch, induced by the [2H6]-Ch injection also returned more rapidly to normal in these animals. This is consistent with peripheral Ch being eliminated faster when the central Ch supply is decreased.
mesh_terms: D000109:Acetylcholine / Q000008:administration & dosage / Q000096:biosynthesis*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002794:Choline / Q000008:administration & dosage / Q000097:blood* / Q000378:metabolism; D003975:Diazepam / Q000494:pharmacology*; D008401:Gas Chromatography-Mass Spectrometry; D051379:Mice
chemical_list: D002794:Choline; D000109:Acetylcholine; D003975:Diazepam