Pharmacological diacylglycerol lipase inhibition impairs contextual fear extinction in mice

Overcoming fear is a key process for our survival. But what happens in the brain when a traumatic memory stays for too long? A study published in Psychopharmacology shows that in mice, blocking the production of a substance called 2-arachidonoylglycerol (2-AG) — an

endocannabinoid essential for communication between brain cells — makes it harder to let go of fear linked to a threatening situation. Scientists found that mice treated with a drug called DO34 learned faster to connect a place with something unpleasant, but then had trouble getting rid of that fear, even when the danger was gone. The results suggest that the endocannabinoid system plays an important role in processing fearful memories, opening new paths to better understand conditions like post-traumatic stress disorder (PTSD) and to develop future treatments.

Ramos-Medina, Liorimar et al. “Pharmacological diacylglycerol lipase inhibition impairs contextual fear extinction in mice.” Psychopharmacology vol. 241,3 (2024): 569-584. doi:10.1007/s00213-023-06523-3