Cannabinoids prevent the development of behavioral and endocrine alterations in a rat model of intense stress

Eti Ganon-Elazar, Irit Akirav

Research output: Contribution to journalArticlepeer-review


Cannabinoids have recently emerged as a possible treatment of stress-and anxiety-related disorders such as post-traumatic stress disorder (PTSD). Here, we examined whether cannabinoid receptor activation could prevent the effects of traumatic stress on the development of behavioral and neuroendocrine measures in a rat model of PTSD, the single-prolonged stress (SPS) model. Rats were injected with the CB1/CB2 receptor agonist WIN55,212-2 (WIN) systemically or into the basolateral amygdala (BLA) at different time points following SPS exposure and were tested 1 week later for inhibitory avoidance (IA) conditioning and extinction, acoustic startle response (ASR), hypothalamic-pituitary-adrenal (HPA) axis function, and anxiety levels. Exposure to SPS enhanced conditioned avoidance and impaired extinction while enhancing ASR, negative feedback on the HPA axis, and anxiety. WIN (0.5 mg/kg) administered intraperitoneally 2 or 24 h (but not 48 h) after SPS prevented the trauma-induced alterations in IA conditioning and extinction, ASR potentiation, and HPA axis inhibition. WIN microinjected into the BLA (5 g/side) prevented SPS-induced alterations in IA and ASR. These effects were blocked by intra-BLA co-administration of the CB1 receptor antagonist AM251 (0.3 ng/side), suggesting the involvement of CB1 receptors. These findings suggest that (i) there may be an optimal time window for intervention treatment with cannabinoids after exposure to a highly stressful event, (ii) some of the preventive effects induced by WIN are mediated by an activation of CB1 receptors in the BLA, and (iii) cannabinoids could serve as a pharmacological treatment of stress-and trauma-related disorders.

Original languageEnglish
Pages (from-to)456-466
Number of pages11
Issue number2
StatePublished - Jan 2012


  • CB1 receptors
  • basolateral amygdala
  • hypothalamic-pituitary-adrenal (HPA) axis
  • inhibitory avoidance extinction
  • post-traumatic stress-disorder
  • single prolonged stress

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Pharmacology


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