Alcohol‐Induced Euphoria Enhanced by Disulfiram and Calcium Carbimide

Brown, Zavie W.; Amit, Zalman; Smith, Brian R.; Sutherland, E. Ann; Selvaggi, Nina

doi:10.1111/j.1530-0277.1983.tb05459.x

Cited by 37 publications

(13 citation statements)

References 18 publications

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“…ACD operant-drinking behaviour is induced and maintained along a relatively long period, which is likely required for exerting pharmacologically significant central effects. On the other hand, our findings are in line with early studies reporting positive euphoric effects following moderate consumption of ethanol in subjects treated with aldehyde dehydrogenase inhibitors, such as disulfiram [76].…”

Section: Discussionsupporting

confidence: 93%

Involvement of Dopamine D2 Receptors in Addictive-Like Behaviour for Acetaldehyde

et al. 2014

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Acetaldehyde, the first metabolite of ethanol, is active in the central nervous system, where it exerts motivational properties. Acetaldehyde is able to induce drinking behaviour in operant-conflict paradigms that resemble the core features of the addictive phenotype: drug-intake acquisition and maintenance, drug-seeking, relapse and drug use despite negative consequences. Since acetaldehyde directly stimulates dopamine neuronal firing in the mesolimbic system, the aim of this study was the investigation of dopamine D2-receptors' role in the onset of the operant drinking behaviour for acetaldehyde in different functional stages, by the administration of two different D2-receptor agonists, quinpirole and ropinirole. Our results show that acetaldehyde was able to induce and maintain a drug-taking behaviour, displaying an escalation during training, and a reinstatement behaviour after 1-week forced abstinence. Acetaldehyde operant drinking behaviour involved D2-receptor signalling: in particular, quinpirole administration at 0.03 mg/kg, induced a significant decrease in the number of lever presses both in extinction and in relapse. Ropinirole, administered at 0.03 mg/kg during extinction, did not produce any modification but, when administered during abstinence, induced a strong decrease in acetaldehyde intake in the following relapse session. Taken together, our data suggest that acetaldehyde exerts its own motivational properties, involving the dopaminergic transmission: indeed, activation of pre-synaptic D2-receptors by quinpirole, during extinction and relapse, negatively affects operant behaviour for acetaldehyde, likely decreasing acetaldehyde-induced dopamine release. The activation of post-synaptic D2-receptors by ropinirole, during abstinence, decreases the motivation to the consecutive reinstatement of acetaldehyde drinking behaviour, likely counteracting the reduction in the dopaminergic tone typical of withdrawal. These data further strengthen the evidence that acetaldehyde may play a crucial role as mediator of ethanol's central effects.

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Section: Discussionsupporting

confidence: 93%

Involvement of Dopamine D2 Receptors in Addictive-Like Behaviour for Acetaldehyde

et al. 2014

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“…161 In agreement with the idea that the effects of ALDH inhibitors are more complicated than previously believed, some individuals have been reported not only to keep drinking alcohol despite being treated with disulfiram but even to find the interaction ethanol-disulfiram pleasurable. [167][168][169][170] These latter results suggest that acetaldehyde might also induce rewarding effects in humans, although the conditions for acetaldehyde accumulation to be rewarding are not known.…”

Section: Pharmacological Manipulations Of Ethanol Metabolism In Humansmentioning

confidence: 98%

Genetic polymorphism in ethanol metabolism: acetaldehyde contribution to alcohol abuse and alcoholism

Quertemont

2004

Mol Psychiatry

151

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Acetaldehyde, the first product of ethanol metabolism, has been speculated to be involved in many pharmacological and behavioral effects of ethanol. In particular, acetaldehyde has been suggested to contribute to alcohol abuse and alcoholism. In the present paper, we review current data on the role of acetaldehyde and ethanol metabolism in alcohol consumption and abuse. Ethanol metabolism involves several enzymes. Whereas alcohol dehydrogenase metabolizes the bulk of ethanol within the liver, other enzymes, such as cytochrome P4502E1 and catalase, also contributes to the production of acetaldehyde from ethanol oxidation. In turn, acetaldehyde is metabolized by the enzyme aldehyde dehydrogenase. In animal studies, acetaldehyde is mainly reinforcing particularly when injected directly into the brain. In humans, genetic polymorphisms of the enzymes alcohol dehydrogenase and aldehyde dehydrogenase are also associated with alcohol drinking habits and the incidence of alcohol abuse. From these human genetic studies, it has been concluded that blood acetaldehyde accumulation induces unpleasant effects that prevent further alcohol drinking. It is therefore speculated that acetaldehyde exerts opposite hedonic effects depending on the localization of its accumulation. In the periphery, acetaldehyde is primarily aversive, whereas brain acetaldehyde is mainly reinforcing. However, the peripheral effects of acetaldehyde might also be dependent upon its peak blood concentrations and its rate of accumulation, with a narrow range of blood acetaldehyde concentrations being reinforcing.

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“…The most important criterion that has to be fulfilled if we are to conclude that AcH per se is involved in the development of ALD is that these damages should correlate with Brown et al (1983) Euphoria associated with Asian flushing Mizoi et al (1983) Positive feelings associated with Asian-American flushing a Wall et al (1992) a Statistically significant comparisons (the other data represent tendencies or case reports). elevated AcH levels.…”

Section: Chronic Pathological Effects Of Alcohol Drinkingmentioning

confidence: 99%

The Role of Acetaldehyde in the Actions of Alcohol (Update 2000)

Eriksson

2001

Alcoholism Clin & Exp Res

228

116

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Background: Recent advances in the field of acetaldehyde (AcH) research have raised the need for a comprehensive review on the role of AcH in the actions of alcohol. This update is an attempt to summarize the available AcH research.Methods: The descriptive part of this article covers not only recent research but also the development of the field. Special emphasis is placed on mechanistic analyses, new hypotheses, and conclusions.Results: Elevated AcH during alcohol intoxication causes alcohol sensitivity, which involves vasodilation associated with increased skin temperature, subjective feelings of hotness and facial flushing, increased heart and respiration rate, lowered blood pressure, sensation of dry mouth or throat associated with bronchoconstriction and allergy reactions, nausea and headache, and also reinforcing reactions like euphoria. These effects seem to involve catecholamine, opiate peptide, prostaglandin, histamine, and/or kinin mechanisms. The contribution of AcH to the pathological consequences of chronic alcohol intake is well established for different forms of cancer in the digestive tract and the upper airways. AcH seems to play a role in the etiology of liver cirrhosis. AcH may have a role in other pathological developments, which include brain damage, cardiomyopathy, pancreatitis, and fetal alcohol syndrome. AcH creates both unpleasant aversive reactions that protect against excessive alcohol drinking and euphoric sensations that may reinforce alcohol drinking. The protective effect of AcH may be used in future treatments that involve gene therapy with or without liver transplantation.Conclusions: AcH plays a role in most of the actions of alcohol. The individual variability in these AcH-mediated actions will depend on the genetic polymorphism, not only for the alcohol and AcHmetabolizing enzymes but also for the target sites for AcH actions. The subtle balance between aversive and reinforcing, protecting and promoting factors will determine the overall behavioral and pathological developments.

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Alcohol‐Induced Euphoria Enhanced by Disulfiram and Calcium Carbimide

Cited by 37 publications

References 18 publications

Involvement of Dopamine D2 Receptors in Addictive-Like Behaviour for Acetaldehyde

Involvement of Dopamine D2 Receptors in Addictive-Like Behaviour for Acetaldehyde

Genetic polymorphism in ethanol metabolism: acetaldehyde contribution to alcohol abuse and alcoholism

The Role of Acetaldehyde in the Actions of Alcohol (Update 2000)

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