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Increased motivation to eat in opiate-withdrawn mice

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Abstract

Rationale

In drug-dependent individuals, the primary excessive motivation is for drugs. Studies also indicate altered interest for “natural” rewarding activities associated with motivational disorders that may be relevant to drug dependence. However, to date, the impact of drug dependence and withdrawal upon motivation for “natural” rewards remains unclear.

Methods and objectives

In the present study, we use a food-driven operant behavior paradigm to assess the impact of opiate intake and withdrawal upon the motivational properties of highly palatable food (HPF) in mice.

Results

Our findings indicate that early (8-h) opiate withdrawal does not affect either the motivational or the discriminative properties of HPF intake. However, starting 32 h after the last morphine injection, opiate withdrawal increases operant behavior aimed at obtaining HPF. The increased HPF-driven behavior lasts at least 12 days following opiate withdrawal, indicating long-lasting effects upon motivation. Using a paradigm of reward contingency reversal, we also address the impact of opiate withdrawal upon cognitive functions. Our results indicate that opiate withdrawal does not affect the ability to learn a new operant rule to obtain HPF. Indeed, opiate withdrawal ameliorates the acquisition of the new HPF-driven operant task, most probably due to the persistent and long-lasting increased motivation. Finally, analysis of ambulatory activity and body weight (BW) changes reveal that motivational and cognitive effects are totally independent of caloric and/or motor effects of opiate dosing and withdrawal.

Conclusions

These results clearly demonstrate that excessive opiate intake and withdrawal produces dramatic and long-lasting motivational disorders relevant to drug dependence.

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Abbreviations

ANOVA:

Analysis of variance

B:

Baseline

BP:

Breakpoint

BW:

Body weight

CRF:

Corticotropin-releasing factor

CTL:

Control

DI:

Discrimination index

FR:

Fixed ratio

HPF:

Highly palatable food

i.p.:

Intraperitoneally

OW:

Opiate withdrawal

PR:

Progressive ratio

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Acknowledgements

The authors were supported by the Université de Bordeaux and the Centre National de la Recherche Scientifique (CNRS). AC was also supported by the Prix Pfizer 2005 de la Société Française d’Endocrinologie. All studies are conducted in accordance with the National Institute of Health Guide for the Care and Use of Laboratory Animals, the European Communities Council Directive of 24 November 1986 (86/609/EEC) and approved by the local Animal Care and Use Committee. The authors declare no conflict of interest.

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Authors and Affiliations

  1. Addicteam, Université de Bordeaux, CNRS UMR 5287, 146 rue Léo Saignat, 33076, Bordeaux, France

    Khalil Rouibi & Angelo Contarino

  2. Unité de Nutrition et Neurosciences, EA 2975, Université de Bordeaux, Bordeaux, France

    Khalil Rouibi & Angelo Contarino

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  1. Khalil Rouibi
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  2. Angelo Contarino
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Correspondence to Angelo Contarino.

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Rouibi, K., Contarino, A. Increased motivation to eat in opiate-withdrawn mice. Psychopharmacology 221, 675–684 (2012). https://doi.org/10.1007/s00213-011-2612-x

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