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Front. Mol. Neurosci. | doi: 10.3389/fnmol.2018.00475

Adenosine A2A receptors in the rat prelimbic medial prefrontal cortex control delay-based cost-benefit decision making

  • 1Centro de Neurociências e Biologia Celular, Universidade de Coimbra, Portugal
  • 2Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul (UFRGS), Brazil
  • 3Departamento de Neurobiologia, Universidade Federal Fluminense, Brazil
  • 4Faculty of Medicine, Universidade Federal do Ceará, Brazil
  • 5Faculdade de Medicina, Universidade de Coimbra, Portugal

Adenosine A2A receptors (A2AR) were recently described to control synaptic plasticity and network activity in the prefrontal cortex (PFC). We now probed the role of these PFC A2AR by evaluating the behavioral performance (locomotor activity, anxiety-related behavior, cost-benefit decision making and working memory) of rats upon viral shA2AR-mediated downregulation of A2AR selectively in the prelimbic medial prefrontal cortex (PLmPFC). The most evident alteration observed in shA2AR-treated rats, when compared to sh-control-treated rats, was a decrease in the choice of the large reward upon an imposed delay of 15 seconds assessed in a T-maze-based cost-benefit decision-making paradigm, suggestive of impulsive decision making. Spontaneous locomotion in the open field was not altered, suggesting no changes in exploratory behavior. Furthermore, rats treated with shA2AR in the PLmPFC also displayed a tendency for higher anxiety levels in the elevated plus maze (less entries in the open arms), but not in the open field test (time spent in the center was not affected). Finally, working memory performance was not significantly altered, as revealed by the spontaneous alternation in the Y-maze test and the latency to reach the platform in the repeated trial Morris water maze. These findings constitute the first direct demonstration of a role of PFC A2AR in the control of behavior in physiological conditions, showing their major contribution for the control of delay-based cost-benefit decisions.

Keywords: adenosine A2A receptors, impulsive choice, prefrontal cortex (PFC), Anxiety, working memory, Cost-benefit decision making

Received: 22 May 2018; Accepted: 05 Dec 2018.

Edited by:

David Blum, INSERM U1172 Centre de Recherche Jean Pierre Aubert, France

Reviewed by:

Ryan K. Bachtell, University of Colorado Boulder, United States
Joana E. Coelho, Institute of Molecular Medicine, Faculty of Medicine, University of Lisbon, Portugal  

Copyright: © 2018 Leffa, Pandolfo, Gonçalves, Machado, De Souza, Real, Silva, Silva, Köfalvi, Cunha and Ferreira. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: PhD. Samira G. Ferreira, Centro de Neurociências e Biologia Celular, Universidade de Coimbra, Coimbra, Portugal,