期刊
MOLECULAR BRAIN
卷 13, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s13041-020-00661-x
关键词
Dopamine; Anterior cingulate cortex; AMPA receptors; D1 receptors; D2 receptors; CFA; Inflammation; Hypersensitivity
资金
- Natural Sciences and Engineering Research Council of Canada (NSERC) [RGPIN-2016-06284]
- Canadian Institutes of Health Research (CIHR) [MOP-13691, PJT-166171]
- Canadian Foundation for Innovation
- Canada Research Chairs program
The release of dopamine (DA) into target brain areas is considered an essential event for the modulation of many physiological effects. While the anterior cingulate cortex (ACC) has been implicated in pain related behavioral processes, DA modulation of synaptic transmission within the ACC and pain related phenotypes remains unclear. Here we characterized a Crispr/Cas9 mediated somatic knockout of the D1 receptor (D1R) in all neuronal subtypes of the ACC and find reduced mechanical thresholds, without affecting locomotion and anxiety. Further, the D1R high-efficacy agonist SKF 81297 and low efficacy agonist (+/-)-SKF-38393 inhibit alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic receptor (AMPAR) currents in the ACC. Paradoxically, the D1R antagonists SCH-23390 and SCH 33961 when co-applied with D1R agonists produced a robust short-term synergistic depression of AMPAR currents in the ACC, demonstrating an overall inhibitory role for D1R ligands. Overall, our data indicate that absence of D1Rs in the ACC enhanced peripheral sensitivity to mechanical stimuli and D1R activation decreased glutamatergic synaptic transmission in ACC neurons.
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