FFAR1シグナルはモノアミン遊離を調節することで情動行動に影響を与える

抄録

The free fatty acid receptor 1 (FFAR1) is suggested to function as a G protein-coupled receptor for medium- to long-chain free fatty acids. We have previously demonstrated that FFAR1 is found to be expressed on noradrenergic and serotonergic neurons in the locus coeruleus and rostral ventromedial medulla (RVM), respectively, and local application of a FFAR1 agonist, GW9508, into these areas evokes a descending endogenous pain control system. These results suggest that one of the functions of FFAR1 in the CNS might control central monoaminergic system.

Thus, to further pursue this hypothesis in this study, we have tested whether FFAR1 plays a role in the regulation of striatal monoamine release. We also analyzed cocaine-induced locomotor stimulation activity in both FFAR1-/- mice and mice treated with a FFAR1 antagonist to evaluate functional significance of FFAR1. Furthermore, we evaluated possible involvement of FFAR1 signaling in the development of negative emotional behaviors after peripheral inflammation and nerve injury in mice. Our data support that FFAR1 signaling is involved in an important mechanism underlying negative emotional behaviors in the inflammatory and neuropathic pain conditions, and enhancement of FFAR1system may be a new strategy to manage at least comorbid pain and negative emotions.