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.
Behav Pharmacol
; 33(8): 551-558, 2022 12 01.
Article
em En
| MEDLINE
| ID: mdl-36256704
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Intoxicação Alcoólica
/
Aldeído-Desidrogenase Mitocondrial
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article