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Acquisition and reconditioning of ethanol-induced conditioned place preference in mice is blocked by the H2O2 scavenger alpha lipoic acid

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Abstract

Rationale

Hydrogen peroxide (H2O2) is the co-substrate used by catalase to metabolize ethanol to acetaldehyde in the brain. This centrally formed acetaldehyde has been involved in several ethanol-related behaviors.

Objectives

The present research evaluated the effect of the H2O2 scavenger, alpha lipoic acid (LA), on the acquisition and reconditioning of ethanol-induced conditioned place preference (CPP).

Methods

Mice received pairings of a distinctive floor stimulus (CS+) associated with intraperitoneal injections of ethanol (2.5 g/kg). On alternate days, animals received pairings of a different floor stimulus (CS−) associated with saline injections. A different group of animals received pairings with the (CS−) associated with saline injections, and on alternate days they received LA (100 mg/kg) injected 30 min prior to ethanol (2.5 g/kg) administration paired with the (CS+). A preference test assessed the effect of LA on the acquisition of ethanol-induced CPP. A similar procedure was followed to study the effect of LA on the acquisition of cocaine- and morphine-induced CPP. A separate experiment evaluated the effect of LA on the reconditioning of ethanol-induced CPP. In addition, we investigated the consequence of LA administration on central H2O2 levels.

Results

LA selectively blocked the acquisition of ethanol-induced CPP. Moreover, this compound impaired the reconditioning of ethanol-induced CPP. Additionally, we found that LA diminished H2O2 levels in the brain.

Conclusions

These data suggest that a decline in H2O2 availability by LA might impede the formation of brain ethanol-derived acetaldehyde by catalase, which results in an impairment of the rewarding properties of ethanol.

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Acknowledgements

This work was supported by grants from MICINN (PSI2011-28934) and from Fundación Caixa Castelló-Bancaixa (P1-1B2011-08), Spain. Juan Carlos Ledesma was supported by a fellowship from Universitat Jaume I (PREDOC/2007/07), Spain.

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  1. Area de Psicobiologia, Universitat Jaume I, Avenida Sos Baynat s/n, 12071, Castellón, Spain

    Juan Carlos Ledesma & Carlos M. G. Aragon

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  1. Juan Carlos Ledesma
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  2. Carlos M. G. Aragon
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Correspondence to Carlos M. G. Aragon.

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Ledesma, J.C., Aragon, C.M.G. Acquisition and reconditioning of ethanol-induced conditioned place preference in mice is blocked by the H2O2 scavenger alpha lipoic acid. Psychopharmacology 226, 673–685 (2013). https://doi.org/10.1007/s00213-012-2831-9

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