Adenosine A2A receptors modulate the dopamine D2 receptor-mediated inhibition of synaptic transmission in the mouse prefrontal cortex.
Eur J Neurosci
; 47(9): 1127-1134, 2018 05.
Article
em En
| MEDLINE
| ID: mdl-29570875
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 (A2A R) also control PFC-related responses and A2A R antagonists are potential anti-psychotic drugs. As tight antagonistic A2A R-D2 R and synergistic A2A R-D1 R interactions occur in other brain regions, we now investigated the crosstalk between A2A R and D1 /D2 R 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 D2 R-like antagonist sulpiride but not by the D1 R antagonist SCH23390 and was mimicked by the D2 R agonist sumanirole, but not by the agonists of either D4 R (A-412997) or D3 R (PD128907). Dopamine inhibition was prevented by the A2A R antagonist, SCH58261, and attenuated in A2A R knockout mice. Accordingly, triple-labelling immunocytochemistry experiments revealed the co-localization of A2A R and D2 R immunoreactivity in glutamatergic (vGluT1-positive) nerve terminals of the PFC. This reported positive A2A R-D2 R interaction controlling PFC synaptic transmission provides a mechanistic justification for the anti-psychotic potential of A2A R antagonists.
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Texto completo:
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores de Dopamina D2
/
Córtex Pré-Frontal
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Agonistas de Dopamina
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Receptor A2A de Adenosina
Limite:
Animals
Idioma:
En
Revista:
Eur J Neurosci
Ano de publicação:
2018
Tipo de documento:
Article