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A critical role for prefrontocortical endocannabinoid signaling in the regulation of stress and emotional behavior.
Neurosci Biobehav Rev. 2014 May; 42:116-31.NB

Abstract

The prefrontal cortex (PFC) provides executive control of the brain in humans and rodents, coordinating cognitive, emotional, and behavioral responses to threatening stimuli and subsequent feedback inhibition of the hypothalamic-pituitary-adrenal (HPA) axis. The endocannabinoid system has emerged as a fundamental regulator of HPA axis feedback inhibition and an important modulator of emotional behavior. However, the precise role of endocannabinoid signaling within the PFC with respect to stress coping and emotionality has only recently been investigated. This review discusses the current state of knowledge regarding the localization and function of the endocannabinoid system in the PFC, its sensitivity to stress and its role in modulating the neuroendocrine and behavioral responses to aversive stimuli. We propose a model whereby steady-state endocannabinoid signaling in the medial PFC indirectly regulates the outflow of pyramidal neurons by fine-tuning GABAergic inhibition. Local activation of this population of CB1 receptors increases the downstream targets of medial PFC activation, which include inhibitory interneurons in the basolateral amygdala, inhibitory relay neurons in the bed nucleus of the stria terminalis and monoamine cell bodies such as the dorsal raphe nucleus. This ultimately produces beneficial effects on emotionality (active coping responses to stress and reduced anxiety) and assists in constraining activation of the HPA axis. Under conditions of chronic stress, or in individuals suffering from mood disorders, this system may be uniquely recruited to help maintain appropriate function in the face of adversity, while breakdown of the endocannabinoid system in the medial PFC may be, in and of itself, sufficient to produce neuropsychiatric illness. Thus, we suggest that endocannabinoid signaling in the medial PFC may represent an attractive target for the treatment of stress-related disorders.

Authors+Show Affiliations

Department of Psychiatry, McGill University, Montreal, QC, Canada. Electronic address: ryan.mclaughlin@mail.mcgill.ca.Department of Cell Biology & Anatomy and Department of Psychiatry, Calgary, AB, Canada; Department of Psychiatry, Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.Department of Psychology, University of British Columbia, Vancouver, BC, Canada.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

24582908

Citation

McLaughlin, Ryan J., et al. "A Critical Role for Prefrontocortical Endocannabinoid Signaling in the Regulation of Stress and Emotional Behavior." Neuroscience and Biobehavioral Reviews, vol. 42, 2014, pp. 116-31.
McLaughlin RJ, Hill MN, Gorzalka BB. A critical role for prefrontocortical endocannabinoid signaling in the regulation of stress and emotional behavior. Neurosci Biobehav Rev. 2014;42:116-31.
McLaughlin, R. J., Hill, M. N., & Gorzalka, B. B. (2014). A critical role for prefrontocortical endocannabinoid signaling in the regulation of stress and emotional behavior. Neuroscience and Biobehavioral Reviews, 42, 116-31. https://doi.org/10.1016/j.neubiorev.2014.02.006
McLaughlin RJ, Hill MN, Gorzalka BB. A Critical Role for Prefrontocortical Endocannabinoid Signaling in the Regulation of Stress and Emotional Behavior. Neurosci Biobehav Rev. 2014;42:116-31. PubMed PMID: 24582908.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A critical role for prefrontocortical endocannabinoid signaling in the regulation of stress and emotional behavior. AU - McLaughlin,Ryan J, AU - Hill,Matthew N, AU - Gorzalka,Boris B, Y1 - 2014/02/26/ PY - 2013/09/25/received PY - 2014/01/31/revised PY - 2014/02/18/accepted PY - 2014/3/4/entrez PY - 2014/3/4/pubmed PY - 2015/7/16/medline KW - Emotional behavior KW - Endocannabinoid system KW - Prefrontal cortex KW - Stress SP - 116 EP - 31 JF - Neuroscience and biobehavioral reviews JO - Neurosci Biobehav Rev VL - 42 N2 - The prefrontal cortex (PFC) provides executive control of the brain in humans and rodents, coordinating cognitive, emotional, and behavioral responses to threatening stimuli and subsequent feedback inhibition of the hypothalamic-pituitary-adrenal (HPA) axis. The endocannabinoid system has emerged as a fundamental regulator of HPA axis feedback inhibition and an important modulator of emotional behavior. However, the precise role of endocannabinoid signaling within the PFC with respect to stress coping and emotionality has only recently been investigated. This review discusses the current state of knowledge regarding the localization and function of the endocannabinoid system in the PFC, its sensitivity to stress and its role in modulating the neuroendocrine and behavioral responses to aversive stimuli. We propose a model whereby steady-state endocannabinoid signaling in the medial PFC indirectly regulates the outflow of pyramidal neurons by fine-tuning GABAergic inhibition. Local activation of this population of CB1 receptors increases the downstream targets of medial PFC activation, which include inhibitory interneurons in the basolateral amygdala, inhibitory relay neurons in the bed nucleus of the stria terminalis and monoamine cell bodies such as the dorsal raphe nucleus. This ultimately produces beneficial effects on emotionality (active coping responses to stress and reduced anxiety) and assists in constraining activation of the HPA axis. Under conditions of chronic stress, or in individuals suffering from mood disorders, this system may be uniquely recruited to help maintain appropriate function in the face of adversity, while breakdown of the endocannabinoid system in the medial PFC may be, in and of itself, sufficient to produce neuropsychiatric illness. Thus, we suggest that endocannabinoid signaling in the medial PFC may represent an attractive target for the treatment of stress-related disorders. SN - 1873-7528 UR - https://www.unboundmedicine.com/medline/citation/24582908/A_critical_role_for_prefrontocortical_endocannabinoid_signaling_in_the_regulation_of_stress_and_emotional_behavior_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0149-7634(14)00027-X DB - PRIME DP - Unbound Medicine ER -