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Role of Endocannabinoid Signaling in Anxiety and Depression

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Behavioral Neurobiology of the Endocannabinoid System

Part of the book series: Current Topics in Behavioral Neurosciences ((CTBN,volume 1))

Abstract

Cannabinoid receptors and their endogenous ligands are located throughout the limbic, or “emotional,” brain, where they modulate synaptic neurotransmission. Converging preclinical and clinical data suggest a role for endogenous cannabinoid signaling in the modulation of anxiety and depression. Augmentation of endocannabinoid signaling (ECS) has anxiolytic effects, whereas blockade or genetic deletion of CB1 receptors has anxiogenic properties. Augmentation of ECS also appears to have anti-depressant actions, and in some assays blockade and genetic deletion of CB1 receptors produces depressive phenotypes. These data provide evidence that ECS serves in an anxiolytic, and possibly anti-depressant, role. These data suggest novel approaches to treatment of affective disorders which could include enhancement of endogenous cannabinoid signaling, and warrant cautious use of CB1 receptor antagonists in patients with pre-existing affective disorders.

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Abbreviations

2AG:

2-Arachidonoylglycerol

5-HT:

5-Hydroxytryptamine, serotonin

ACC:

Anterior cingulate cortex

AEA:

Anandamide

BLA:

Basolateral amygdala

CCK:

Cholecystokinin

CUS:

Chronic exposure to an unpredictable and variable set of stressors

ECS:

Endocannabinoid signaling

ECT:

Electroconvulsive therapy

FAAH:

Fatty acid amide hydrolase

HPA:

Hypothalamus–pituitary–adrenal

KO:

Knockout

PFC:

Prefrontal cortex

PTSD:

Post-traumatic stress disorder

PVN:

Paraventricular nucleus

SSRI:

Selective serotonin re-uptake inhibitors

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Acknowledgements

CJH was supported during the writing of this review by Research for a Healthier Tomorrow, a component of the Advancing a Healthier Wisconsin endowment at the Medical College of Wisconsin and NIH grant R21 DA022439.

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Authors and Affiliations

  1. Department of Pharmacology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USA

    Sachin Patel & Cecilia J. Hillard

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  1. Sachin Patel
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  2. Cecilia J. Hillard
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Correspondence to Cecilia J. Hillard .

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Editors and Affiliations

  1. Queen's Medical Centre, University of Nottingham, Nottingham, NG7 2UH, United Kingdom

    Dave Kendall

  2. Queen's Medical Centre, University of Nottingham, Nottingham, NG7 2UH, United Kingdom

    Stephen Alexander

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Patel, S., Hillard, C.J. (2009). Role of Endocannabinoid Signaling in Anxiety and Depression. In: Kendall, D., Alexander, S. (eds) Behavioral Neurobiology of the Endocannabinoid System. Current Topics in Behavioral Neurosciences, vol 1. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-88955-7_14

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