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Ethanol-induced conditioned place preference, but not aversion, is blocked by treatment with d-penicillamine, an inactivation agent for acetaldehyde

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Abstract

Rationale

There is evidence to suggest that acetaldehyde is involved in the control of ethanol-seeking behavior and reward. d-penicillamine, a thiol amino acid, is a highly selective agent for the inactivation of acetaldehyde. Previous studies from our laboratory have demonstrated that d-penicillamine prevents both behavioral stimulation induced by ethanol and acetaldehyde-produced locomotor depression in mice.

Objectives

The contribution of ethanol-derived acetaldehyde to the affective effects of ethanol (preference and aversion) was assessed using an unbiased place conditioning design.

Methods

Male mice received four pairings of a distinctive floor stimulus (CS+: GRID+ or HOLE+) with injections of saline and ethanol (2 g/kg) given before (preference) or after (aversion) the 5-min exposure to the place conditioning apparatus. A different floor stimulus (CS−: GRID− or HOLE−), associated with saline-saline injections on alternate days, was presented. For a different group of animals, the pairings with the CS+ were associated with saline and ethanol injections, but on alternate days, they received d-penicillamine (50 or 75 mg/kg) and ethanol injections paired with the CS−floor stimulus. A 60-min preference test was carried out 24 h after the last conditioning trial. A similar procedure was followed to test the effect of d-penicillamine on morphine (16 mg/kg) and cocaine-induced (20 mg/kg) conditioned place preference (CPP).

Results

CPP and conditioned place aversion (CPA) were observed for ethanol, but d-penicillamine only blocked CPP. d-penicillamine, by itself, did not produce either rewarding or aversive effects. CPP observed for morphine and cocaine was unaffected by d-penicillamine pretreatment.

Conclusions

The results of the present study suggest that the selective inactivation of acetaldehyde blocked the rewarding, but not aversive, effects of ethanol and support the role of this ethanol metabolite in the affective properties of ethanol.

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Acknowledgements

This study was supported by grants from Generalitat Valenciana (05I151.01/2) and from Red de Trastornos Adictivos, Ministerio de Sanidad y Consumo (G03/005), Spain. The authors gratefully acknowledge the technical assistance provided by Alicia Dosda and Gemma Caballer and the linguistic revision by Fiona McClelland. Animal procedures were performed in accordance with the European Community Council directive (86/609/ECC).

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  1. Área de Psicobiología, Universitat Jaume I, Campus de Riu Sec, Apartat 8029AP, Castellò, 12071, Spain

    Laura Font, Carlos M. G. Aragon & Marta Miquel

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  1. Laura Font
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  2. Carlos M. G. Aragon
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  3. Marta Miquel
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Correspondence to Marta Miquel.

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Font, L., Aragon, C.M.G. & Miquel, M. Ethanol-induced conditioned place preference, but not aversion, is blocked by treatment with d-penicillamine, an inactivation agent for acetaldehyde. Psychopharmacology 184, 56–64 (2006). https://doi.org/10.1007/s00213-005-0224-z

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