Alpha-Lipoic Acid Reduces Ethanol Self-Administration in Rats

Abstract

These results support that ALA may have a potential use in alcoholism treatment.

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

“…In addition, a wealth of experimental evidence supports that the motivational effects of ethanol are mediated by its metabolism into ACD either in the periphery or in the brain. Accordingly, this has been demonstrated by inhibiting the production of ACD in the periphery (inhibition of ADH), by inhibiting the generation of brain ACD (inhibition of brain catalase) or by reducing ACD bioavailability (Font et al, 2006a,b; Peana et al, 2008a, 2009, 2010a, 2013a,b; Enrico et al, 2009; Sirca et al, 2011; Correa et al, 2012). All these observations support the tenet that the generation of central and peripheral, but not peripherally accumulated (Escrig et al, 2012), ACD actively participates in the positive motivational properties of ethanol and raise the possibility that its role can be exploited to devise novel pharmacological approaches that target alcohol abuse related problems.…”

“…By reacting with H 2 O 2 , brain catalase forms compound I (the catalase-H 2 O 2 system), which is able to oxidize ethanol into ACD (Pastor et al, 2002; Ledesma and Aragon, 2012). Recently we showed that the H 2 O 2 scavenging agent, alpha lipoic acid, dose-dependently reduces the maintenance and break point of oral ethanol self-administration under a progressive ratio schedule as well as the reinstatement of ethanol seeking behavior without suppressing saccharin self-administration (Peana et al, 2013b). On a similar vein, a recent study by Ledesma and Aragon (2013) demonstrated that alpha lipoic acid reduces the acquisition and reconditioning of ethanol-induced CPP in mice.…”

Glutathione and redox signaling in substance abuse

“…These findings from the human genetic and alcohol-preferring rat studies on GST are intriguing, but a direct relationship between alcohol consumption and GST has not been empirically tested. Two recent studies have demonstrated that the antioxidants α-lipoic acid and ebselen significantly reduce alcohol consumption and reinstatement of alcohol-seeking behavior in rats and mice [100,101]. In both studies, saccharin intake was not affected by α-lipoic acid or ebselen suggesting a selective role for this system in alcohol reward.…”

Mystic Acetaldehyde: The Never-Ending Story on Alcoholism

“…By these experiments, it was shown that the intraperitoneal administration of alpha lipoic acid, a radical scavenger that interferes with catalase-H 2 O 2 activity (Ledesma et al, 2012), decreases maintenance, reinstatement and progressive ratio of oral operant ethanol self-administration. Likewise, L-cysteine acts also during the acquisition phase of ethanol and acetaldehyde self-administration (Peana et al, 2012, 2013b) with the acetaldehyde-binding property of cysteine being probably responsible for these effects. Likewise, Peana et al (2015) have reported that D-penicillamine, a synthetic amino acid that strongly binds acetaldehyde, inhibits the acquisition of oral ethanol self-administration.…”

“…A rapidly growing body of evidence on the efficacy of radical scavengers and antioxidants such as L-cysteine (Peana et al, 2010a, 2012, 2013b), alpha lipoic acid (Ledesma et al, 2012; Peana et al, 2013a) and N-acetyl cysteine (Quintanilla et al, 2016), both on CPP experiments and in different phases (not only during the acquisition) of operant self-administration as well as on voluntary ethanol intake could be referred to the observation that a neuro-inflammatory process could be responsible of ethanol excessive taking (Montesinos et al, 2016). Indeed, the metabolism of ethanol into acetaldehyde and acetate is associated to the production of ROS that accentuate the oxidative state of cells promoting oxidative damage, neuronal injury and neurodegeneration.…”