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New operant model of reinstatement of food-seeking behavior in mice

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Abstract

Rationale

A major problem in treating obesity is the high rate of relapse to abnormal food-taking behavior when maintaining diet.

Objectives

The present study evaluates the reinstatement of extinguished palatable food-seeking behavior induced by cues previously associated with the palatable food, re-exposure to this food, or stress. The participation of the opioid and dopamine mechanisms in the acquisition, extinction, and cue-induced reinstatement was also investigated.

Materials and methods

C57BL/6 mice were first trained on a fixed-ratio-1 schedule of reinforcement to obtain chocolate-flavored pellets during 20 days, which was associated to a stimulus light. Operant behavior was then extinguished during 20 daily sessions. mRNA levels of opioid peptide precursors and dopamine receptors were evaluated in the brain by in situ hybridization and RT-PCR techniques.

Results

A reinstatement of food-seeking behavior was only obtained after exposure to the food-associated cue. A down-regulation of prodynorphin mRNA was found in the dorsal striatum and nucleus accumbens after the acquisition, extinction, and reinstatement of the operant behavior. Extinction and reinstatement of this operant response enhanced proenkephalin mRNA in the dorsal striatum and/or the nucleus accumbens core. Down-regulation of D2 receptor expression was observed in the dorsal striatum and nucleus accumbens after reinstatement. An up-regulation of PDYN mRNA expression was found in the hypothalamus after extinction and reinstatement.

Conclusions

This study provides a new operant model in mice for the evaluation of food-taking behavior and reveals specific changes in the dopamine and opioid system associated to the behavioral responses directed to obtain a natural reward.

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Abbreviations

Arc:

Activity-regulated cytoskeleton-associated protein

BDNF:

Brain-derived neurotrophic factor

Cartpt:

Prepropeptide cart

Crh:

Corticotropin-releasing hormone

Ghrl:

Ghrelin

Hcrt:

Hypocretin

PENK:

Proenkephalin

PDYN:

Prodynorphin and POMC, proopiomelanocortin

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Acknowledgements

This work was supported by the USA National Institutes of Health—National Institute of Drug Abuse (NIH-NIDA) (No. 1R01-DA01 6768-0111), the DG Research of the European Commission (PHECOMP, No. LHSM-CT-2007-037669 and GENADDICT, No. LSHM-CT-2004-05166), the Spanish ‘Instituto de Salud Carlos III’ (No. RD06/001/001), the Spanish ‘Ministerio de Educación y Ciencia’ (No. SAF2007-64062), the Catalan Government (SGR2009-00131), the ICREA Foundation (ICREA Academia-2008), the statutory activity funds of the Institute of Pharmacology, Polish Academy of Sciences and the Polish Ministry of Science and Higher Education subsidiary grant 478/6. PR UE/2007/7. E.M.G. was supported by a post-doctoral fellowship from the Spanish ‘Instituto de Salud Carlos III’.

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Authors and Affiliations

  1. Departament de Ciencies Experimentals i de la Salut, Universitat Pompeu Fabra, PRBB, C/Dr. Aiguader 88, 08003, Barcelona, Spain

    Elena Martín-García, Aurelijus Burokas & Rafael Maldonado

  2. Institute of Pharmacology, Polish Academy of Sciences, ul. Smetna 12, 31-343, Krakow, Poland

    Elzbieta Kostrzewa, Agnieszka Gieryk, Michal Korostynski, Barbara Ziolkowska, Barbara Przewlocka & Ryszard Przewlocki

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  1. Elena Martín-García
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  2. Aurelijus Burokas
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  9. Rafael Maldonado
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Correspondence to Rafael Maldonado.

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Martín-García, E., Burokas, A., Kostrzewa, E. et al. New operant model of reinstatement of food-seeking behavior in mice. Psychopharmacology 215, 49–70 (2011). https://doi.org/10.1007/s00213-010-2110-6

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