Behavioral Characterization of Acetaldehyde in C57BL/6J Mice: Locomotor, Hypnotic, Anxiolytic and Amnesic Effects

Overview

Journal Psychopharmacology (Berl)

Specialty Pharmacology

Date 2004 May 26

PMID 15160264

Citations 23

Authors

Etienne Quertemont

Sophie Tambour

Pascale Bernaerts

Sergey M Zimatkin

Ezio Tirelli

Affiliations

Soon will be listed here.

Abstract

Rationale: Acetaldehyde, the first metabolite of ethanol, was recently suggested to contribute to many behavioral effects of ethanol, although few studies have directly investigated the behavioral effects of acetaldehyde itself.

Objectives: The aim of the present study was to characterize the locomotor, hypnotic, anxiolytic-like and amnesic effects of acetaldehyde in C57BL/6J mice.

Methods: Increasing doses of acetaldehyde (0-300 mg/kg) were injected intraperitoneally and their effects on a series of representative behaviors were investigated. The locomotor effects of acetaldehyde were measured in activity boxes. The duration of the loss of righting reflex was used as an index of the hypnotic effects of acetaldehyde. The anxiolytic-like effects of acetaldehyde were tested with an elevated plus-maze and the amnesic effects with the one-trial passive avoidance test. Finally, brain and blood acetaldehyde concentrations were assessed.

Results: Acetaldehyde induced a significant hypolocomotor effect at 170 mg/kg and higher doses. In addition, the hypnotic effects of acetaldehyde were demonstrated by a loss of righting reflex after the administration of 170 and 300 mg/kg acetaldehyde. The elevated plus-maze showed that acetaldehyde does not possess anxiolytic-like properties. Finally, acetaldehyde (100-300 mg/kg) dose-dependently altered memory consolidation as shown by a reduced performance in the passive avoidance test.

Conclusions: The present results show that acetaldehyde induces sedative, hypnotic and amnesic effects, whereas it is devoid of stimulant and anxiolytic-like properties in C57BL/6J mice. However, the behavioral effects of acetaldehyde after intraperitoneal administration were apparent at very high brain concentrations. The present results also indicate that acetaldehyde is unlikely to be involved in the anxiolytic properties of ethanol in mice.

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References

Quertemont E, Escarabajal M, de Witte P . Role of catalase in ethanol-induced conditioned taste aversion: a study with 3-amino-1,2,4-triazole. Drug Alcohol Depend. 2003; 70(1):77-83. DOI: 10.1016/s0376-8716(02)00341-1. View

Zimatkin S, Liopo A, Satanovskaya V, Bardina And L, Deitrich R . Relationship of brain ethanol metabolism to the hypnotic effect of ethanol. II: Studies in selectively bred rats and mice. Alcohol Clin Exp Res. 2001; 25(7):982-8. View

Randall C, Carpenter J, Lester D, Friedman H . Ethanol-induced mouse strain differences in locomotor activity. Pharmacol Biochem Behav. 1975; 3(3):533-5. DOI: 10.1016/0091-3057(75)90069-6. View

Quertemont E . Discriminative stimulus effects of ethanol with a conditioned taste aversion procedure: lack of acetaldehyde substitution. Behav Pharmacol. 2003; 14(4):343-50. DOI: 10.1097/01.fbp.0000082130.08343.47. View

Prunell M, Escorihuela R, Fernandez-Teruel A, Nunez J, Tobena A . Differential interactions between ethanol and Ro 15-4513 on two anxiety tests in rats. Pharmacol Biochem Behav. 1994; 47(1):147-51. DOI: 10.1016/0091-3057(94)90124-4. View

Escarabajal M, de Witte P, Quertemont E . Role of acetaldehyde in ethanol-induced conditioned taste aversion in rats. Psychopharmacology (Berl). 2003; 167(2):130-6. DOI: 10.1007/s00213-003-1427-9. View

Nuutinen H, Lindros K, Salaspuro M . Determinants of blood acetaldehyde level during ethanol oxidation in chronic alcoholics. Alcohol Clin Exp Res. 1983; 7(2):163-8. DOI: 10.1111/j.1530-0277.1983.tb05432.x. View

Eriksson C, Sippel H, FORSANDER O . The determination of acetaldehyde in biological samples by head-space gas chromatography. Anal Biochem. 1977; 80(1):116-24. DOI: 10.1016/0003-2697(77)90631-5. View

Escarabajal D, Miquel M, Aragon C . A psychopharmacological study of the relationship between brain catalase activity and ethanol-induced locomotor activity in mice. J Stud Alcohol. 2000; 61(4):493-8. DOI: 10.15288/jsa.2000.61.493. View

10.

Zimatkin S, Liopo A, Slychenkov V, Deitrich R . Relationship of brain ethanol metabolism to the hypnotic effect of ethanol. I: Studies in outbred animals. Alcohol Clin Exp Res. 2001; 25(7):976-81. View

11.

Aragon C, Spivak K, Amit Z . Effect of 3-amino-1,2,4-triazole on ethanol-induced narcosis, lethality and hypothermia in rats. Pharmacol Biochem Behav. 1991; 39(1):55-9. DOI: 10.1016/0091-3057(91)90397-k. View

12.

Frye G, Breese G . An evaluation of the locomotor stimulating action of ethanol in rats and mice. Psychopharmacology (Berl). 1981; 75(4):372-9. DOI: 10.1007/BF00435856. View

13.

Eriksson C, Sippel H . The distribution and metabolism of acetaldehyde in rats during ethanol oxidation-I. The distribution of acetaldehyde in liver, brain, blood and breath. Biochem Pharmacol. 1977; 26(3):241-7. DOI: 10.1016/0006-2952(77)90310-0. View

14.

Aragon C, Spivak K, Amit Z . Blockade of ethanol induced conditioned taste aversion by 3-amino-1,2,4-triazole: evidence for catalase mediated synthesis of acetaldehyde in rat brain. Life Sci. 1985; 37(22):2077-84. DOI: 10.1016/0024-3205(85)90579-x. View

15.

Zimatkin S, Deitrich R . Ethanol metabolism in the brain. Addict Biol. 2016; 2(4):387-400. DOI: 10.1080/13556219772444. View

16.

Correa M, Sanchis-Segura C, Aragon C . Influence of brain catalase on ethanol-induced loss of righting reflex in mice. Drug Alcohol Depend. 2001; 65(1):9-15. DOI: 10.1016/s0376-8716(01)00142-9. View

17.

Zimatkin S, Lindros K . Distribution of catalase in rat brain: aminergic neurons as possible targets for ethanol effects. Alcohol Alcohol. 1996; 31(2):167-74. DOI: 10.1093/oxfordjournals.alcalc.a008128. View

18.

Quertemont E, DE Witte P . Conditioned stimulus preference after acetaldehyde but not ethanol injections. Pharmacol Biochem Behav. 2001; 68(3):449-54. DOI: 10.1016/s0091-3057(00)00486-x. View

19.

Castellano C, Populin R . Effect of ethanol on memory consolidation in mice: antagonism by the imidazobenzodiazepine Ro 15-4513 and decrement by familiarization with the environment. Behav Brain Res. 1990; 40(1):67-72. DOI: 10.1016/0166-4328(90)90044-f. View

20.

Bernaerts P, Tirelli E . Facilitatory effect of the dopamine D4 receptor agonist PD168,077 on memory consolidation of an inhibitory avoidance learned response in C57BL/6J mice. Behav Brain Res. 2003; 142(1-2):41-52. DOI: 10.1016/s0166-4328(02)00371-6. View