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Integration of Endocannabinoid Signaling into the Neural Network Regulating Stress-Induced Activation of the Hypothalamic–Pituitary–Adrenal Axis

  • Boris B. GorzalkaEmail author
  • Matthew N. Hill
Chapter
Part of the Current Topics in Behavioral Neurosciences book series (CTBN, volume 1)

Abstract

The evidence that has been gathered to date strongly argues for an inhibitory role of endocannabinoid (ECB) signaling in regulating HPA axis activity. Under basal conditions, ECB signaling appears to be a driving force in the maintenance of low HPA axis activity, as disruption of CB1 receptor activity results in basal hyperactivity of the HPA axis. Under conditions of acute stress, ECB signaling likewise appears to constrain activation of the HPA axis, possibly via both distal regulation of incoming amygdalar inputs and local regulation of excitatory input to CRF neurosecretory cells in the PVN. ECB neurotransmission is, in turn, modulated by stress, possibly acting as either a “gatekeeper” of the HPA axis, or a recovery system aimed at limiting HPA axis activity. Consistently, pharmacological enhancement of ECB signaling attenuates stress-induced HPA axis activity while impairment of CB1 receptor signaling results in an exaggerated cellular and neuroendocrine response to stress. Additionally, under conditions of repeated stress, a progressive increase in limbic 2AG/CB1 receptor signaling contributes to the development and expression of neuroendocrine habituation.

Ultimately, these data demonstrate that the ECB system is likely to be an integral player in the neuronal response and plasticity to stress. The relevance of this relationship has not been fully explored with respect to both normal homeostasis and pathological states characterized by alterations in HPA axis function, but will be a focus of future research.

Keywords

Cannabinoid Anandamide 2-AG FAAH Stress PVN HPA axis Corticosterone Amygdala Adrenal 

Abbreviations

2AG

2-Arachidonoylglycerol

ACTH

Adrenocorticotropic hormone

AEA

Anandamide

BLA

Basolateral nucleus of the amygdala

CeA

Central nucleus of the amygdala

CRF

Corticotrophin-releasing factor

ECB

Endocannabinoid

FAAH

Fatty acid amide hydrolase

GH

Growth hormone

HPA

Hypothalamic–pituitary–adrenal

MeA

Medial amygdala

MGL

Monoacylglycerol lipase

mPFC

Medial prefrontal cortex

PAG

Periaqueductal gray

PVN

Paraventricular nucleus of the hypothalamus

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© Springer-Verlag Berlin Heidelberg 2009

Authors and Affiliations

  1. 1.Department of PsychologyUniversity of British ColumbiaVancouverCanada

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