Adenosine A2A receptors modulate the dopamine D2 receptor‐mediated inhibition of synaptic transmission in the mouse prefrontal cortex |
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| Authors: | Joana I. Real Ana Patrícia Simões Rodrigo A. Cunha Samira G. Ferreira Daniel Rial |
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| Affiliation: | 1. CNC‐Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal;2. Faculty of Medicine, University of Coimbra, Coimbra, Portugal |
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| Abstract: | Prefrontal cortex (PFC) circuits are modulated by dopamine acting on D1‐ and D2‐like receptors, which are pharmacologically exploited to manage neuropsychiatric conditions. Adenosine A2A receptors (A2AR) also control PFC‐related responses and A2AR antagonists are potential anti‐psychotic drugs. As tight antagonistic A2AR–D2R and synergistic A2AR–D1R interactions occur in other brain regions, we now investigated the crosstalk between A2AR and D1/D2R controlling synaptic transmission between layers II/III and V in mouse PFC coronal slices. Dopamine decreased synaptic transmission, a presynaptic effect based on the parallel increase in paired‐pulse responses. Dopamine inhibition was prevented by the D2R‐like antagonist sulpiride but not by the D1R antagonist SCH23390 and was mimicked by the D2R agonist sumanirole, but not by the agonists of either D4R (A‐412997) or D3R (PD128907). Dopamine inhibition was prevented by the A2AR antagonist, SCH58261, and attenuated in A2AR knockout mice. Accordingly, triple‐labelling immunocytochemistry experiments revealed the co‐localization of A2AR and D2R immunoreactivity in glutamatergic (vGluT1‐positive) nerve terminals of the PFC. This reported positive A2AR–D2R interaction controlling PFC synaptic transmission provides a mechanistic justification for the anti‐psychotic potential of A2AR antagonists. |
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| Keywords: | A2A receptor adenosine D1 receptor D2 receptor dopamine prefrontal cortex receptor interaction synaptic transmission |
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