MS21570 as a GPR171 antagonist based on its ability to block,with an IC50 of 220 Nm,that reduces anxiety-like behavior and fear conditioning in mice.

GPR171:220 nM

The role of GPR171 in anxiety-like behavior or fear conditioning was evaluated following systemic or intra-BLA administration of MS21570, as well as following lentiviral-mediated knockdown of GPR171 in the BLA.?Systemic administration of MS21570 attenuates anxiety-like behavior while intra-BLA administration or knockdown of GPR171 in the BLA reduces anxiety-like behavior and fear conditioning.

Mice were habituated to the testing room 1?h prior to each experiment.?Behaviors were videotaped and analyzed using Noldus EthoVision XT or by an experimenter blinded to the treatment groups.?Mice were injected with MS21570 (5?mg/kg) 15?min prior to elevated plus maze, open field, forced swim, and contextual fear conditioning.?For microinjection studies, MS21570 was injected 10?min prior to testing and immediately following the contextual fear conditioning.?A counterbalanced within-subjects design was used when appropriate (battery of anxiety tests).