Aldehyde dehydrogenase 2–associated changes in pharmacokinetics, locomotor function and peripheral glutamic acid and gamma-aminobutyric acid levels during acute alcohol intoxication in male mice. Issue 8 (18th October 2022)

• Record Type: Journal Article
• Authors: Li, Songfan; Zheng, Yuzi; Xiao, Li; Lan, Shengnan; Xiang, Jin; Liao, Linchuan; Lin, Yao; Ye, Yi
• Is Part Of: Behavioural pharmacology. Volume 33:Issue 8(2022)
• Page Start: 551
• Page End: 558
• Publication Date: 2022-10-18
• Subjects: acute alcohol intoxication -- aldehyde dehydrogenase 2 -- gamma-aminobutyric acid -- glutamic acid -- psychomotor function -- rat; Psychopharmacology -- Periodicals; Nervous System -- drug effects -- Periodicals; Behavior -- drug effects -- Periodicals; 615.78
• DOI: 10.1097/FBP.0000000000000702
• Languages: English
• ISSNs: 0955-8810

Abstract

Abstract : The insufficiency of human aldehyde dehydrogenase 2 (ALDH2) has been consistently associated with high blood acetaldehyde levels and impaired locomotor function during acute alcohol intoxication. The ALDH2-associated change in peripheral glutamic acid (Glu) and gamma-aminobutyric acid (GABA) levels and its correlation with pharmacokinetics and psychomotor function remain unclear. In this study, ALDH2*2 mice were used to build an acute alcohol intoxication model after intraperitoneal administration. The blood ethanol and acetaldehyde concentrations were analyzed to generate concentration-time curves at two doses of alcohol (2.0 and 4.0 g/kg). The dose of 4.0 g/kg was selected in accordance with the preliminary behavioral evaluation result to perform the following behavioral tests (e.g. the rotarod test, the open field test, and the Y-maze test), so as to assess locomotor activity, anxiety and cognitive ability. Plasma Glu and GABA levels were determined through enzyme-linked immunosorbent assays. The results suggested that the ALDH2*2 mice had highly accumulated acetaldehyde levels, impaired locomotor activity and anxiety-like emotion but unimpaired cognitive function, compared to the wild type (WT) mice. The plasma Glu level and the ratio of Glu/GABA in the alcohol-treated WT and ALDH2*2 groups decreased from 2 to 5 h after intraperitoneal administration, whereas the GABA level did not change significantly. The blood alcohol concentration in the WT and ALDH2*2 mice was positively correlated with plasma Glu level, whereas the blood acetaldehyde level was found as the opposite. We speculate that the decline degree of Glu/GABA ratio could be associated with psychomotor retardation and needs to be further investigated.