An acetaldehyde-sequestering agent inhibits appetitive reinforcement and behavioral stimulation induced by ethanol in preweanling rats

Abstract

Ethanol's motivational consequences have been related to the actions of acetaldehyde, a metabolic product of ethanol oxidation. The present study assessed the role of acetaldehyde in the motivational effects of ethanol on pre-weanling rats. In Experiment 1 pups (postnatal days 13-14, PD 13-14) were given systemic administration of d-penicillamine (DP, a drug that sequesters acetaldehyde: 0, 25, 50 or 75 mg/kg) before pairings of 1.0 g/kg ethanol and a rough surface (sandpaper, conditioned stimulus, CS). At test, pups given sandpaper-ethanol pairings exhibited greater preference for the CS than unpaired controls, but this preference was not expressed by pups given DP. Pre-training administration of 25 or 50 mg/kg DP completely blocked the expression of ethanol-mediated appetitive conditioning. D-penicillamine did not alter blood ethanol levels. Subsequent experiments revealed that ethanol-induced activation was blocked by central (intra-cisterna magna injections, volume: 1 μl, dose: 0 or 75 μg) but not systemic treatment with DP (0, 25, 50 or 75 mg/kg; ip). These results indicate that: (a) pre-weanling rats are sensitive to the reinforcing effect of ethanol, and (b) that this effect is associated with the motor activating effect of the drug. These effects seem to be mediated by the first metabolite of ethanol, acetaldehyde.

Reduction in Central H2O2Levels Prevents Voluntary Ethanol Intake in Mice: A Role for the Brain Catalase-H2O2System in Alcohol Binge Drinking

“…For this reason, it has been proposed that brain-EtOH-derived acetaldehyde could play a role in some of the psychopharmacological effects caused by EtOH. In agreement to this, it has been observed that administration of acetaldehyde chelating agents, such as D-penicillamine and L-cysteine, prevents a wide range of EtOH-elicited behaviors, including EtOH intake (Font et al, 2005(Font et al, , 2006Mart ı-Prats et al, 2010;Pautassi et al, 2010;Peana et al, 2010). The results obtained in this study indicated that H 2 O 2 levels are critical to EtOH intake.…”

Salsolinol Stimulates Dopamine Neurons in Slices of Posterior Ventral Tegmental Area Indirectly by Activating μ-Opioid Receptors

“…Many laboratories have tested the role of the ethanol metabolite acetaldehyde, by impairing its formation (see Correa et al, 2011 for review) or using acetaldehyde sequestering agents such as D-penicilamine (Enrico et al, 2009;Martí-Prats et al, 2010;Pautassi et al, 2010). All of these in vivo studies have shown that the behavioral, neurochemical, and electrophysiological properties of ethanol are impaired when acetaldehyde, and conse- quently salsolinol, cannot be formed (Enrico et al, 2009;Martí-Prats et al, 2010).…”

Elucidating the biological basis for the reinforcing actions of alcohol in the mesolimbic dopamine system: the role of active metabolites of alcohol

“…For instance, administration of either D-penicillamine or L-cysteine effectively reduced EtOH consumption and decreased EtOH conditioned place preference (CPP) in rats (Font et al, 2006b; Diana et al, 2008; Peana et al, 2008). Intra-cisterna magna injections of D-pennicillamine acted to block EtOH- and/or ACD appetitive conditioning to a surrogate nipple in newborn rats (March et al, 2013) and induced locomotor activity and tactile stimulus preference in preweanling rats (Pautassi et al, 2011). Mice exhibit a decrease in EtOH CPP and a reduction in EtOH-induced motor depression when treated with D-penicillamine (Font et al, 2005, 2006a).…”

“…Adult rats peripherally treated with ACD exhibit a dose-dependent preference to a discrete olfactory stimulus (Quertemont and DeWitte, 2001). Rat pups exhibited a significant preference to an olfactory cue previously paired with ACD exposure (March et al, 2013) while pre-weanling rats exhibited an ACD-dependent stimulation of locomotor activity and tactile stimulus preference following EtOH administration (Nizhnikov et al, 2007; Pautassi et al, 2011). ACD has been shown to dose-dependently alter locomotor activity in adult animals as well.…”