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Adenosine A(2A) receptors (A(2A)Rs) were recently described to control synaptic plasticity and network activity in the prefrontal cortex (PFC). We now probed the role of these PFC A(2A)R by evaluating the behavioral performance (locomotor activity, anxiety-related behavior, cost-benefit decision making and working memory) of rats upon downregulation of A(2A)R selectively in the prelimbic medial PFC (PLmPFC) via viral small hairpin RNA targeting the A(2A)R (shA(2A)R). The most evident alteration observed in shA(2A)R-treated rats, when compared to sh-control (shCTRL)-treated rats, was a decrease in the choice of the large reward upon an imposed delay of 15 s 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 shA(2A)R 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 A(2A)R in the control of behavior in physiological conditions, showing their major contribution for the control of delay-based cost-benefit decisions.


Leffa, Douglas T.;  Pandolfo, Pablo;  Goncalves, Nelio;  Machado, Nuno J.;  de Souza, Carolina M.;  Real, Joana I.;  Silva, Antonio C.;  Silva, Henrique B.;  Kofalvi, Attila;  Cunha, Rodrigo A.;  Ferreira, Samira G.

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