Over the past 2 decades, there has been rapidly growing interest in the role of the
endocannabinoid (eCB) system in the regulation of stress and emotional processes.
Several lines of converging evidence provide strong evidence that eCB signaling is
a key player in these processes. First, genetic ablation or pharmacologic antagonism
of the cannabinoid type 1 receptor (CB1R) results in exaggerated neuroendocrine and behavioral responses to acute stress
(
1
). More so, sustained disruption of CB1R signaling produces an array of neurobiological changes consistent with alterations
seen after chronic stress or in mood disorders, such as reductions in neurotrophin
levels, neurogenesis and dendritic complexity, and increased levels of central neuroinflammation
(
2
,
3
). Second, facilitation of eCB signaling can dampen the impact of both acute and chronic
stress on almost every variable examined, including alterations in anxiety, reward
sensitivity, hyperalgesia, morphologic changes in the amygdala, and hippocampal synaptic
plasticity (
1
). Third, the eCB system is highly sensitive to stress exposure. Specifically, under
conditions of acute stress, the eCB system plays an important buffering role by limiting
the magnitude of the stress response and facilitating recovery to basal function after
cessation of stress exposure (
1
). However, under conditions of chronic stress, the eCB system appears to “collapse”
in the sense that CB1Rs downregulate and lose their ability to modulate the synaptic release of neurotransmitters,
such as glutamate and gamma-aminobutyric acid (
1
).To read this article in full you will need to make a payment
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References
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Article info
Publication history
Accepted:
March 15,
2016
Received:
March 15,
2016
Identification
Copyright
© 2016 Society of Biological Psychiatry.
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Access this article on ScienceDirectLinked Article
- Anxiety, Stress, and Fear Response in Mice With Reduced Endocannabinoid LevelsBiological PsychiatryVol. 79Issue 10
- PreviewDisruption of the endocannabinoid system through pharmacological or genetic invalidation of cannabinoid CB1 receptors has been linked to depression in humans and depression-like behaviors in mice. The two main endogenous cannabinoids, anandamide and 2-arachidonoyl glycerol (2-AG), are produced on demand from phospholipids. The pathways and enzymes involved in endocannabinoid biosynthesis thus play a major role in regulating the activity of this system. This study investigates the role of the main 2-AG producing enzyme diacylglycerol lipase α (DAGL-α).
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