Endocannabinoid modulation of defensive state transitions to innate and learned threat.
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 (eC...
| Publicado en: | Psychopharmacology Vol. 243; no. 2; pp. 325 - 339 |
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| Autores principales: | , , , , , |
| Formato: | Journal Article |
| Publicado: |
Springer Nature
Feb2026
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=191574307&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 191574307 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00333158 EJD jtl: Psychopharmacology issn: 00333158 maglogo: N pubinfo: dt: Feb2026 vid: 243 iid: 2 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 191574307 185349045 10.1007/s00213-025-06812-z 191574307 ppf: 325 ppct: 14 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Endocannabinoid modulation of defensive state transitions to innate and learned threat. aug: au: Loomba, Niharika Cao, Anyu Charles, Senna Kandil, Isaac Kwon, Michelle Patel, Sachin affil: https://ror.org/02vm5rt34 Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN, USA sug: ab: 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 enhanced freezing to early cues and promoted active responses during cues associated with heightened threat imminence. In the looming shadow paradigm, 2-AG depletion biased defensive behavior toward freezing and increased time spent in a safe zone, suggesting a shift toward passive responses. These findings demonstrate that 2-AG signaling critically regulates the balance and transitions between passive and active defensive strategies in both learned and innate fear contexts. Thus, 2-AG plays a key role in the scaling of defensive response transitions and the promotion of active defensive responses to threats. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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