title: Cannabinoids prevent the development of behavioral and endocrine alterations in a rat model of intense stress.
abstract: 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 μg/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.
authors.affiliation: Department of Psychology, University of Haifa, Haifa, Israel.
authors.forename: Eti
authors.initials: E
authors.lastname: Ganon-Elazar
authors.forename: Irit
authors.initials: I
authors.lastname: Akirav
mesh_terms: D000679:Amygdala / Q000187:drug effects; D000818:Animals; D001007:Anxiety / Q000188:drug therapy* / Q000517:prevention & control*; D001362:Avoidance Learning / Q000187:drug effects; D048588:Benzoxazines / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D063386:Cannabinoid Receptor Agonists; D063387:Cannabinoid Receptor Antagonists; D002186:Cannabinoids / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D003907:Dexamethasone; D004195:Disease Models, Animal; D005108:Extinction, Psychological / Q000187:drug effects; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D007274:Injections, Intraperitoneal; D008297:Male; D008845:Microinjections; D009025:Morpholines / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D009281:Naphthalenes / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D010880:Piperidines / Q000494:pharmacology; D010912:Pituitary-Adrenal Function Tests / Q000379:methods; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects; D055139:Sensory Gating / Q000187:drug effects; D013313:Stress Disorders, Post-Traumatic / Q000188:drug therapy* / Q000517:prevention & control*; D013312:Stress, Physiological / Q000187:drug effects
chemical_list: D048588:Benzoxazines; D063386:Cannabinoid Receptor Agonists; D063387:Cannabinoid Receptor Antagonists; D002186:Cannabinoids; D009025:Morpholines; D009281:Naphthalenes; D010880:Piperidines; D011720:Pyrazoles; C103505:AM 251; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D003907:Dexamethasone