Effects of Diazepam on Blood Choline and Acetylcholine Turnover in Brain of Mice.

Autor: Lundgren, G., Nordgren, I., Karlén, B., Jacobsson, G.
Zdroj: Pharmacology & Toxicology; 1987, Vol. 60 Issue 2, p96-99, 4p
Abstrakt: 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 beeing eliminated faster when the central Ch supply is decreased. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index