Relationship of Brain Ethanol Metabolism to the Hypnotic Effect of Ethanol. I: Studies in Outbred Animals

Зиматкин, С. М.; Liopo, Anton V.; Slychenkov, V. S.; Deitrich, Richard A.

doi:10.1111/j.1530-0277.2001.tb02305.x

Cited by 20 publications

(5 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…At the highest doses (4.0 g/kg and higher), ethanol induces a significant and long lasting LORR in mice (Correa et al 2001b;Zimatkin et al 2001a). In the present study, acetaldehyde produces a similar pattern of results.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, previous studies reported evidence that acetaldehyde is involved in ethanol-induced narcosis (Zimatkin et al 2001a), locomotor stimulation (Escarabajal et al 2000;Correa et al 2001a), conditioned taste aversion (Aragon et al 1985;Quertemont et al 2003), reinforcement (Quertemont and De Witte 2001) and lethality (Aragon et al 1991). However, most of these studies investigated the behavioral effects of acetaldehyde by pharmacological alterations of ethanol metabolism, although the specificity of several of the pharmacological substances that were used has been questioned (Hunt 1996).…”

Section: Introductionmentioning

confidence: 97%

See 1 more Smart Citation

Behavioral characterization of acetaldehyde in C57BL/6J mice: locomotor, hypnotic, anxiolytic and amnesic effects

et al. 2004

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

Behavioral characterization of acetaldehyde in C57BL/6J mice: locomotor, hypnotic, anxiolytic and amnesic effects

et al. 2004

Self Cite

View full text Add to dashboard Cite

show abstract

“…QUESTIONS REGARDING ETHANOL metabolism by brain tissue have recurred over the past 30 years (Quertemont, 2004; Tabakoff and Gelpke, 1975; Zimatkin et al, 2001). These questions have not only centered on a curiosity regarding the tissue distribution and characteristics of ethanol metabolizing enzymes, but have also been central to theories regarding the etiology of excessive drinking, with respect to the reinforcing (Smith et al, 1997) and aversive (Blum and Trachtenberg, 1988) properties of ethanol.…”

Section: Alcohol and Aldehyde Metabolizing Genes Represented On Affymentioning

confidence: 99%

Gene Array Profiles of Alcohol and Aldehyde Metabolizing Enzymes in Brains of C57BL/6 and DBA/2 Mice

Bhave¹,

Hoffman²,

Lassen³

et al. 2006

Alcoholism Clin & Exp Res

Self Cite

View full text Add to dashboard Cite

show abstract

“…The concentrations of AA in liver, blood, and brain that occur with drinking lie in the micromolar range (23, 24), in contrast to millimolar levels of Etoh and Ac, and AA rapidly disappears after sample collection due to its volatility. EtOH oxidation and the formation of AA have been measured in brain homogenates (11,(27)(28)(29)(30) and cell cultures (31). In a novel approach, Zimatkin and Buben made the measurement in living brain by intraventricular perfusion (9) of anesthetized rats with 180 mM Etoh and measured AA concentrations rising to ∼50 μM in the perfusate (23).…”

mentioning

confidence: 99%

Oxidation of ethanol in the rat brain and effects associated with chronic ethanol exposure

Wang

Jiang³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

It has been reported that chronic and acute alcohol exposure decreases cerebral glucose metabolism and increases acetate oxidation. However, it remains unknown how much ethanol the living brain can oxidize directly and whether such a process would be affected by alcohol exposure. The questions have implications for reward, oxidative damage, and long-term adaptation to drinking. One group of adult male Sprague-Dawley rats was treated with ethanol vapor and the other given room air. After 3 wk the rats received i.v. [2-13 C]ethanol and [1, 2-13 C 2 ]acetate for 2 h, and then the brain was fixed, removed, and divided into neocortex and subcortical tissues for measurement of 13 C isotopic labeling of glutamate and glutamine by magnetic resonance spectroscopy. Ethanol oxidation was seen to occur both in the cortex and the subcortex. In ethanol-naïve rats, cortical oxidation of ethanol occurred at rates of 0.017 ± 0.002 μmol/min/g in astroglia and 0.014 ± 0.003 μmol/min/g in neurons, and chronic alcohol exposure increased the astroglial ethanol oxidation to 0.028 ± 0.002 μmol/min/g (P = 0.001) with an insignificant effect on neuronal ethanol oxidation. Compared with published rates of overall oxidative metabolism in astroglia and neurons, ethanol provided 12.3 ± 1.4% of cortical astroglial oxidation in ethanol-naïve rats and 20.2 ± 1.5% in ethanol-treated rats. For cortical astroglia and neurons combined, the ethanol oxidation for naïve and treated rats was 3.2 ± 0.3% and 3.8 ± 0.2% of total oxidation, respectively. 13C labeling from subcortical oxidation of ethanol was similar to that seen in cortex but was not affected by chronic ethanol exposure.T he liver is the major organ for the oxidation of ethanol (Etoh) (1, 2), followed by the stomach and other organs. Acetate (Ac) generated from Etoh by the liver is consumed by the brain (3, 4), where it replaces a significant portion of cerebral glucose metabolism in humans and animals (5-8), either decreasing glucose consumption directly or compensating for glucose consumption decreased by some other effect. However, the brain may also oxidize Etoh (9-14), and that capacity is important with respect to several perspectives. The first step of Etoh oxidation generates acetaldehyde (AA), which is toxic, reactive, and potentially carcinogenic. AA is aversive systemically, as has been observed from the unpleasant effects of disulfuram, an inhibitor of AA dehydrogenase, but it has been shown to be rewarding in parts of the brain (12,15,16) especially in the posterior ventral tegmental area (17-19) by activating dopamine neurons (20)(21)(22). The liver maintains circulating levels of AA at levels of 20-155 μM (23, 24), and AA has been reported not to penetrate the blood-brain barrier or to penetrate very slowly (23,25). Thus, if the brain can oxidize Etoh, then intracerebral AA may mediate behavioral, neurochemical, and toxic effects of Etoh in the brain, possibly playing a role in the development of alcohol dependence (6,16,26).AA is difficult to measure in living systems. The ...

show abstract

Relationship of Brain Ethanol Metabolism to the Hypnotic Effect of Ethanol. I: Studies in Outbred Animals

Abstract: This study is a direct demonstration of the positive correlation between ethanol-derived acetaldehyde accumulation in vitro in the brain and a central (behavioral) effect of alcohol in outbred rats and mice in vivo.

Cited by 20 publications

References 33 publications

Behavioral characterization of acetaldehyde in C57BL/6J mice: locomotor, hypnotic, anxiolytic and amnesic effects

Behavioral characterization of acetaldehyde in C57BL/6J mice: locomotor, hypnotic, anxiolytic and amnesic effects

Gene Array Profiles of Alcohol and Aldehyde Metabolizing Enzymes in Brains of C57BL/6 and DBA/2 Mice

Oxidation of ethanol in the rat brain and effects associated with chronic ethanol exposure

Contact Info

Product

Resources

About