Behavioral and biochemical evidence of the role of acetaldehyde in the motivational effects of ethanol

Abstract

Since Chevens' report, in the early 50's that his patients under treatment with the aldehyde dehydrogenase inhibitor, antabuse, could experience beneficial effects when drinking small volumes of alcoholic beverages, the role of acetaldehyde (ACD) in the effects of ethanol has been thoroughly investigated on pre-clinical grounds. Thus, after more than 25 years of intense research, a large number of studies have been published on the motivational properties of ACD itself as well as on the role that ethanol-derived ACD plays in the effects of ethanol. Accordingly, in particular with respect to the motivational properties of ethanol, these studies were developed following two main strategies: on one hand, were aimed to challenge the suggestion that also ACD may exert motivational properties on its own, while, on the other, with the aid of enzymatic manipulations or ACD inactivation, were aimed to test the hypothesis that ethanol-derived ACD might have a role in ethanol motivational effects. Furthermore, recent evidence significantly contributed to highlight, as possible mechanisms of action of ACD, its ability to commit either dopaminergic and opioidergic transmission as well as to activate the Extracellular signal Regulated Kinase cascade transduction pathway in reward-related brain structures. In conclusion, and despite the observation that ACD seems also to have inherited the elusive nature of its parent compound, the behavioral and biochemical evidence reviewed points to ACD as a neuroactive molecule able, on its own and as ethanol metabolite, to exert motivational effects.

Effects of Withania somnifera on oral ethanol self-administration in rats

“…This possibility originates from the observation that several studies point (i) to the brain catalase-H 2 O 2 enzymatic system as a suitable pathway that oxidizes ethanol into acetaldehyde (Aragon et al, 1991;Aragon and Amit, 1992) and (ii) to the actions of acetaldehyde itself, of ethanol-derived acetaldehyde (Correa et al, 2012;Peana and Acquas, 2013), as well as of the product of condensation between dopamine and acetaldehyde, salsolinol (Melis et al, 2013), on dopamine neurons in the VTA as responsible for the reinforcing properties of ethanol (Rodd et al, 2008;Hipólito et al, 2011). Thus, on the basis of the observation that W. somnifera has long been suggested to exert its neuroprotective properties by acting as a free radical scavenger (Bhattacharya et al, 2001) and as an antihydrogen peroxide-mediated mechanism (Kumar et al, 2010), it appears reasonable to hypothesize that WSE may also interfere with the motivational effects of ethanol that require the involvement of central catalase activity (Font et al, 2008;Melis et al, 2013;.…”

Lipids and Oxidative Stress Associated with Ethanol‐Induced Neurological Damage

“…Salsolinol has been identified in the brain and cerebrospinal fluid of patients with Parkinson disease, and it has been proposed to increase ROS production along with a reduction of glutathione [ 108 ], as well as reducing intracellular ATP and thereby acting as an inhibitor of mitochondrial energy supply. Thus, acetaldehyde reinforces its own effects or enhances the addictive action of ethanol [ 109 , 110 ].…”

Mystic Acetaldehyde: The Never-Ending Story on Alcoholism

“…Followers of the first view suggest that ethanol exerts its properties within the brain by affecting numerous neurotransmitter systems, that there is no significant evidence that its metabolites cross the blood brain barrier and that the metabolites occur for only short periods to mediate the effects of ethanol intoxication. The working hypothesis that envisions ethanol as a pro-drug, on the other hand, suggests that its activating and reinforcing properties are supported by the central actions of its metabolites (Deng and Deitrich, 2008 ; Deitrich, 2011 ; Karahanian et al, 2011 ; Correa et al, 2012 ; Hipólito et al, 2012 ; Peana and Acquas, 2013 ; Israel et al, 2015 ), no matter if generated centrally or peripherally. In the latter case, according to the pro-drug theory, acetaldehyde’s plasma levels, following ethanol intake, would reach concentrations sufficient to significantly affect its targets within the central nervous system (CNS).…”