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Choosing voluntary exercise over sucrose consumption depends upon dopamine transmission: effects of haloperidol in wild type and adenosine A2AKO mice

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Abstract

Rationale

Mesolimbic dopamine (DA) regulates behavioral activation and effort-related decision-making in motivated behaviors. Mesolimbic DA D2 receptors are co-localized with adenosine A2A receptors, and they interact in an antagonistic manner.

Objectives

A T-maze task was developed to assess dopaminergic involvement in preference between a reinforcer that involves vigorous voluntary activity (running wheel) and a reinforcer that requires minimal behavioral activation (sucrose pellets). Haloperidol (D2 antagonist) was administered to adenosine A2A receptor knockout (A2AKO) and wild-type (WT) littermate controls to assess the involvement of these two receptors in the selection of running wheel activity versus sucrose consumption.

Results

Under control conditions, mice spent more time running and less time eating. In WT mice, haloperidol reduced time running but actually increased time-consuming sucrose. However, A2AKO mice did not show the haloperidol-induced shift from running wheel activity to sucrose intake. Prefeeding reduced sucrose consumption in the T-maze in both strains, indicating that this paradigm is sensitive to motivational devaluation. Haloperidol increased c-Fos immunoreactivity in anterior cingulate cortex (ACg) and nucleus accumbens (Acb) core of WT but not KO mice.

Conclusions

These results indicate that after DA antagonism, the preference for vigorous physical activity is reduced, while palatable food selection increases. Adenosine A2A receptor deletion provides resistance to these effects of D2 receptor antagonism. These two receptors in Acb core and ACg seem to be involved in the regulation of the intrinsic reinforcing characteristics of voluntary exercise but not in the regulation of the primary reinforcing characteristics of palatable sedentary reinforcers.

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Acknowledgments

This work was supported by a grant to Mercè Correa from Pla Promoció Investigació UJI (P1.1 A 2013-01), to John D. Salamone from the National Institute of Mental Health (MH078023), and to Olga Valverde from Ministery of Economy, Spain (SAF-2013-41761-R). Personal grants were awarded to Marta Pardo (Predoc-UJI/ 2007/43), Noemí San Miguel (Predoc-UJI/2012/28), and Laura Lopez-Cruz (FPU AP2010-3793, Ministerio de Educación, Spain).

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Authors and Affiliations

  1. Department of Psychobiology, Universitat Jaume I, Castelló, Spain

    Mercè Correa, Marta Pardo, Pilar Bayarri, Laura López-Cruz & Noemí San Miguel

  2. Department of Experimental and Health Sciences, Universitat Pompeu Fabra and IMIM-Hospital del Mar Research Institute, Barcelona, Spain

    Olga Valverde

  3. Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Université Libre de Bruxelles, IRIBHM, Bruxelles, Belgium

    Catherine Ledent

  4. Department of Psychology, University of Connecticut, Storrs, CT, USA

    John D. Salamone

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  1. Mercè Correa
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  2. Marta Pardo
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  3. Pilar Bayarri
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  4. Laura López-Cruz
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Correspondence to Mercè Correa or John D. Salamone.

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Correa, M., Pardo, M., Bayarri, P. et al. Choosing voluntary exercise over sucrose consumption depends upon dopamine transmission: effects of haloperidol in wild type and adenosine A2AKO mice. Psychopharmacology 233, 393–404 (2016). https://doi.org/10.1007/s00213-015-4127-3

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  • DOI: https://doi.org/10.1007/s00213-015-4127-3

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