Inhibiting the enzyme fatty-acid amide hydrolase (FAAH) with URB597, which prevents the breakdown of the endocannabinoid anandamide, produces antidepressant-like effects in mice and rats. URB597 reduced immobility in the tail-suspension and forced-swim tests, and increased firing of serotonin and norepinephrine neurons in brain regions linked to mood. These effects required CB1 receptor activation and were accompanied by higher brain anandamide levels. Unlike direct THC-like drugs, URB597 showed no rewarding or abuse-related effects. The findings suggest FAAH inhibition as a potential target for antidepressant drugs without the psychotropic side effects of cannabis.
Propofol, a common general anesthetic, strengthens emotional memory consolidation when given immediately after a stressful event, unlike other sedatives. In rats trained on an avoidance task, anesthetic doses of propofol administered right after training led to significantly longer retention of the fearful memory 48 hours later, compared to a vehicle control. This memory-enhancing effect was blocked by a cannabinoid receptor antagonist, indicating it depends on the endocannabinoid system. Delayed administration of propofol or immediate post-training administration of midazolam or pentobarbital did not affect memory retention. The findings suggest propofol's influence on emotional memory may explain its association with traumatic memories after surgery.