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Endocannabinoid modulation of defensive state transitions to innate and learned threat.


ABSTRACT: A hallmark of many psychiatric disorders is maladaptive and heightened fear responses to non-threatening stimuli. Adaptive defensive responses to threats involve transitions between passive behaviors, such as freezing, and active escape strategies, such as darting or fleeing. The endocannabinoid (eCB) system, particularly 2-arachidonoylglycerol (2-AG), plays a crucial role in modulating fear and stress responses. However, the extent to which 2-AG influences defensive behavioral state transitions to fear responses remains unclear. To address this, we investigated the role of 2-AG in shaping defensive behaviors to learned and innate threats using pharmacological manipulations in both the serial compound stimulus (SCS) and the looming shadow paradigm. During SCS, inhibition of 2-AG synthesis

SUBMITTER: Loomba N 

PROVIDER: S-EPMC12904945 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature