Concurrent administration of diethyldithiocarbamate and 4-methylpyrazole enhances ethanol-induced locomotor activity: the role of brain ALDH

Escarabajal, Ma Dolores; Aragón, Carlos M.G.

doi:10.1007/s00213-001-0991-0

Cited by 18 publications

(8 citation statements)

References 27 publications

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“…The conventional view that ethanol metabolism to acetaldehyde is carried out by class I liver alcohol dehydrogenase (ADH1; Haseba and Ohno, 2010), was obtained following animal (Bradford et al, 1993a,b; Escarabajal and Aragon, 2002; Peana et al, 2008) and human (Blomstrand and Theorell, 1970; Crow and Hardman, 1989; Sarkola et al, 2002) experiments with specific inhibitors (pyrazoles) of ADH (Figure 1). In humans, ADH1 is further classified into three subcategories, ADH1A, 1B and 1C (all inhibited by 4-methylpyrazole, 4-MP), which are the main ADHs for the oxidation of ethanol (Hempel et al, 1984).…”

Section: Peripheral Generation Of Acetaldehydementioning

confidence: 99%

“…Otherwise, the oxidation of ethanol to acetaldehyde can occur in the brain through pathways that involve catalase, CYP2E1 and ADH (Hipólito et al, 2007; Figure 2). In particular, although under appropriate conditions the latter seems to represent a main pathway of ethanol metabolism in the liver, it has been attributed a minor contribution in the brain as indicated by biochemical (Zimatkin et al, 2006) and behavioral studies (Escarabajal and Aragon, 2002). Interestingly, a recent study, showed that ADH, whose several isoforms, such as ADH1, 3 and 4, have been found in the mammal brain (Boleda et al, 1989; Galter et al, 2003; Hipólito et al, 2007), is related to the enhancement of voluntary ethanol intake in University of Chile Bibulous (UChB) rats, bred for their high alcohol preference, after an injection into the ventral tegmental area (VTA) of a lentiviral vector encoding for ADH (Karahanian et al, 2011).…”

Section: Central Generation Of Acetaldehydementioning

confidence: 99%

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Mystic Acetaldehyde: The Never-Ending Story on Alcoholism

Peana

Sánchez-Catalán

Hipólito

et al. 2017

Front. Behav. Neurosci.

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After decades of uncertainties and drawbacks, the study on the role and significance of acetaldehyde in the effects of ethanol seemed to have found its main paths. Accordingly, the effects of acetaldehyde, after its systemic or central administration and as obtained following ethanol metabolism, looked as they were extensively characterized. However, almost 5 years after this research appeared at its highest momentum, the investigations on this topic have been revitalized on at least three main directions: (1) the role and the behavioral significance of acetaldehyde in different phases of ethanol self-administration and in voluntary ethanol consumption; (2) the distinction, in the central effects of ethanol, between those arising from its non-metabolized fraction and those attributable to ethanol-derived acetaldehyde; and (3) the role of the acetaldehyde-dopamine condensation product, salsolinol. The present review article aims at presenting and discussing prospectively the most recent data accumulated following these three research pathways on this never-ending story in order to offer the most up-to-date synoptic critical view on such still unresolved and exciting topic.

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Section: Peripheral Generation Of Acetaldehydementioning

confidence: 99%

Section: Central Generation Of Acetaldehydementioning

confidence: 99%

Mystic Acetaldehyde: The Never-Ending Story on Alcoholism

Peana

Sánchez-Catalán

Hipólito

et al. 2017

Front. Behav. Neurosci.

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“…Indeed, there was evidence that catalase could oxidize brain EtOH to AcH in vivo after alcohol consumption [18]. By using catalase inhibitors or inducers, further studies demonstrated that AcH formation can be modified after EtOH addition [9,[20][21][22][23][24][25]. Lower levels of AcH were also found in catalase deficient (acatalasemic) mice when brain homogenates were incubated with EtOH, compared to those of normal mice [24,25].…”

Section: Brain Acetaldehyde Productionmentioning

confidence: 99%

Putative Role of Brain Acetaldehyde in Ethanol Addiction

Deng¹,

Deitrich²

2008

CDAR

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The putative contribution of brain acetaldehyde (AcH) to ethanol (EtOH) tolerance and dependence (addiction) is reviewed. Although the role of AcH in EtOH addiction has been controversial, there are data showing a relationship. AcH can be formed in the brain tissues through the peroxidatic activity of catalase and by oxidation via other oxidizing enzymes such as cytochrome P-4502E1. Significant formation of AcH occurs in vitro in brain tissue at concentrations of EtOH that can be achieved by voluntary consumption of EtOH by rodents. AcH itself possesses reinforcing properties, which suggests that some of the behavioral pharmacological effects attributed to EtOH may be a result of the formation of AcH, and supports the involvement of AcH in EtOH addiction. Modulation of aldehyde dehydrogenase (ALDH) and brain catalase activity can change EtOH-related addictive behaviors presumably by changing AcH levels. Moreover, some condensation reaction products of AcH may promote some actions of EtOH and its consumption. On the basis of the findings, it can be concluded that AcH may mediate some of the CNS actions of EtOH including tolerance and dependence, although further exploration the involvement of AcH in EtOH addiction is warranted.

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“…The most widely employed strategy to demonstrate the involvement of ACD in the motivational and reinforcing effects of ethanol has been, for years, the pharmacological manipulation of the enzyme system activity implicated in the brain metabolism of this drug. For instance, modulating catalase (Correa et al, 1999, 2004; Sanchis-Segura et al, 1999a,b; Arizzi-LaFrance et al, 2006; Font et al, 2008), cytocrome P-4502E1 (Hipolito et al, 2009; Ledesma et al, 2014) or alcohol dehydrogenase (Escarabajal and Aragon, 2002) brain activity.…”

Section: Introductionmentioning

confidence: 99%

Pre-Clinical Studies with D-Penicillamine as a Novel Pharmacological Strategy to Treat Alcoholism: Updated Evidences

Orrico

Martí‐Prats

Cano-Cebrián

et al. 2017

Front. Behav. Neurosci.

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Ethanol, as other drugs of abuse, is able to activate the ventral tegmental area dopamine (VTA-DA) neurons leading to positively motivational alcohol-seeking behavior and use, and, ultimately to ethanol addiction. In the last decades, the involvement of brain-derived acetaldehyde (ACD) in the ethanol actions in the mesolimbic pathway has been widely demonstrated. Consistent published results have provided a mechanistic support to the use of ACD inactivating agents to block the motivational and reinforcing properties of ethanol. Hence, in the last years, several pre-clinical studies have been performed in order to analyze the effects of the sequestering ACD agents in the prevention of ethanol relapse-like drinking behavior as well as in chronic alcohol consumption. In this sense, one of the most explored interventions has been the administration of D-Penicillamine (DP). These pre-clinical studies, that we critically summarize in this article, are considered a critical step for the potential development of a novel pharmacotherapeutic strategy for alcohol addiction treatment that could improve the outcomes of current ones. Thus, on one hand, several experimental findings provide the rationale for using DP as a novel therapeutic intervention alone and/or in combination to prevent relapse into alcohol seeking and consumption. On the other hand, its effectiveness in reducing voluntary ethanol consumption in long-term experienced animals still remains unclear. Finally, this drug offers the additional advantage that has already been approved for use in humans, hence it could be easily implemented as a new therapeutic intervention for relapse prevention in alcoholism.

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Concurrent administration of diethyldithiocarbamate and 4-methylpyrazole enhances ethanol-induced locomotor activity: the role of brain ALDH

Abstract: These data suggest that brain ALDH may contribute to the effects of ethanol on locomotor activity. This role of the enzyme ALDH in some of the psychopharmacological effects of ethanol may be a result of its ability to regulate levels of acetaldehyde in brain.

Cited by 18 publications

References 27 publications

Mystic Acetaldehyde: The Never-Ending Story on Alcoholism

Mystic Acetaldehyde: The Never-Ending Story on Alcoholism

Putative Role of Brain Acetaldehyde in Ethanol Addiction

Pre-Clinical Studies with D-Penicillamine as a Novel Pharmacological Strategy to Treat Alcoholism: Updated Evidences

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