Cannabinoids and traumatic stress modulation of contextual fear extinction and GR expression in the amygdala-hippocampal-prefrontal circuit

Summary Considerable evidence suggests that cannabinoids modulate the behavioral and physiological response to stressful events. We have recently shown that activating the cannabinoid system using the CB1/CB2 receptor agonist WIN55,212-2 (WIN) in proximity to exposure to single-prolonged stress (SPS...

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Published in:Psychoneuroendocrinology 2013-09, Vol.38 (9), p.1675-1687
Main Authors: Ganon-Elazar, Eti, Akirav, Irit
Format: Article
Language:English
Subjects:
Adult and adolescent clinical studies
Amygdala - drug effects
Amygdala - physiopathology
Animals
Anxiety disorders. Neuroses
Behavioral psychophysiology
Benzoxazines - pharmacology
Biological and medical sciences
Cannabinoids
Cannabinoids - pharmacology
CB1 receptors
Contextual fear extinction
Electroshock
Endocrinology & Metabolism
Extinction, Psychological - drug effects
Extinction, Psychological - physiology
Fear - drug effects
Fear - physiology
Freezing Reaction, Cataleptic - drug effects
Freezing Reaction, Cataleptic - physiology
Fundamental and applied biological sciences. Psychology
Glucocorticoid receptors
Hippocampus - drug effects
Hippocampus - physiopathology
Hormones and behavior
Hypothalamo-Hypophyseal System - physiopathology
Male
Medical sciences
Microinjections
Mifepristone - pharmacology
Models, Psychological
Morpholines - pharmacology
Naphthalenes - pharmacology
Piperidines - pharmacology
Pituitary-Adrenal System - physiopathology
Post traumatic stress disorder
Prefrontal Cortex - drug effects
Prefrontal Cortex - physiopathology
Psychiatry
Psychology. Psychoanalysis. Psychiatry
Psychology. Psychophysiology
Psychopathology. Psychiatry
Pyrazoles - pharmacology
Rats
Rats, Sprague-Dawley
Receptor, Cannabinoid, CB1 - drug effects
Receptor, Cannabinoid, CB1 - physiology
Receptor, Cannabinoid, CB2 - drug effects
Receptor, Cannabinoid, CB2 - physiology
Receptors, Glucocorticoid - antagonists & inhibitors
Receptors, Glucocorticoid - biosynthesis
Receptors, Glucocorticoid - genetics
Receptors, Glucocorticoid - physiology
Single prolonged stress
Stress, Psychological - physiopathology
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Summary:Summary Considerable evidence suggests that cannabinoids modulate the behavioral and physiological response to stressful events. We have recently shown that activating the cannabinoid system using the CB1/CB2 receptor agonist WIN55,212-2 (WIN) in proximity to exposure to single-prolonged stress (SPS), a rat model of emotional trauma, prevented the stress-induced enhancement of acoustic startle response, the impairment in avoidance extinction and the enhanced negative feedback on the hypothalamic-pituitary-adrenal (HPA) axis ( Ganon-Elazar and Akirav, 2012 ). Some of the effects were found to be mediated by CB1 receptors in the basolateral amygdala (BLA). Here we examined whether cannabinoid receptor activation in a putative brain circuit that includes the BLA, hippocampus and prefrontal cortex (PFC), could prevent the effects of traumatic stress on contextual fear extinction and alterations in glucocorticoid receptor (GR) protein levels. We found that: (i) SPS impaired contextual fear extinction tested one week after trauma exposure and that WIN prevented the stress-induced impairment of extinction when microinjected immediately after trauma exposure into the BLA or hippocampus (5 μg), but not when microinjected into the PFC, (ii) the ameliorating effects of WIN on contextual extinction were prevented by blocking GRs in the BLA and hippocampus, and (iii) SPS up regulated GRs in the BLA, PFC and hippocampus and systemic WIN administration (0.5 mg/kg) after trauma exposure normalized GR levels in the BLA and hippocampus, but not in the PFC. Cannabinoid receptor activation in the aftermath of trauma exposure may regulate the emotional response to the trauma and prevent stress-induced impairment of extinction and GR up regulation through the mediation of CB1 receptors in the BLA and hippocampus. Taken together, the findings suggest that the interaction between the cannabinoid and glucocorticoid systems is crucial in the modulation of emotional trauma.
ISSN:0306-4530
1873-3360
DOI:10.1016/j.psyneuen.2013.01.014