Endocannabinoids, cannabinoids and the regulation of anxiety

Petrie, Gavin N; Nastase, Andrei S.; Aukema, Robert J.; Hill, Matthew N.

doi:10.1016/j.neuropharm.2021.108626

Cited by 51 publications

(30 citation statements)

References 367 publications

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“…A high level of PPI was previously seen in S1 mice in relation to BL6 strain ( Millstein et al, 2006 ), although no direct comparison between strains was performed in this study. Considering that the ECS participates in the regulation of anxiety ( Petrie et al, 2021 ), extinction of aversive memories ( Mizuno and Matsuda, 2021 ) and sensorimotor gating ( Dissanayake et al, 2013 ), this neuromodulatory system could contribute to the phenotypic alterations observed in S1 mice. Interestingly, we found important differences in the mRNA levels of various components of the ECS between S1 and BL6 mice in several brain areas.…”

Section: Discussionmentioning

confidence: 99%

“…This neuromodulatory system plays a crucial role in different neurophysiological processes. Disturbances in the ECS, mainly related to CB1R dysfunction, are associated with several psychiatric conditions such as posttraumatic stress disorder ( Mayo et al, 2022 ), anxiety ( Petrie et al, 2021 ) or schizophrenia ( Leweke et al, 2018 ), among others. Interestingly, CB2R, initially regarded as a peripheral cannabinoid receptor, has been recently involved in the regulation of different neurobiological processes including cognition and mood-related (anxiety, depression) behaviors ( Banaszkiewicz et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

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CB2 cannabinoid receptor expression is increased in 129S1/SvImJ mice: behavioral consequences

et al. 2022

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Genetic and environmental factors are implicated in the etiology of neuropsychiatric diseases. Inbred mouse strains, including the 129S1/SvImJ (S1), constitute important models to study the influence of genetic factors in these conditions. S1 mice displayed anxiogenic-like behavior, impaired fear extinction, and increased prepulse inhibition (PPI) of startle reflex compared to C57BL/6J (BL6) mice. Given the role played by the endocannabinoid system (ECS) in these responses, we evaluated the expression of the ECS components in different brain regions in S1 mice. Gene expression levels of the cannabinoid type-1 and type-2 receptors (CB1R and CB2R) and the endocannabinoid metabolizing enzymes varied depending on the brain region evaluated. Notably, CB2R expression markedly increased in the amygdala, prefrontal cortex and hippocampus in S1 mice. Moreover, CB2R blockade with SR144528 partially rescued the anxiogenic phenotype in S1 mice, while CB2R activation with JWH133 potentiated the deficits in fear extinction and the PPI of startle reflex in this mouse strain. These data suggest that CB2R is involved in the behavioral alterations observed in S1 mice and underline the importance of this cannabinoid receptor subtype in the regulation of certain central nervous system disorders.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

CB2 cannabinoid receptor expression is increased in 129S1/SvImJ mice: behavioral consequences

et al. 2022

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“…Substantial evidence shows that eCB systems play a key role in the modulation of stress signaling, wherein disruptions of eCB signaling can facilitate anxiety-like states. 146 CB 1 receptors are expressed in high or moderate densities across many regions involved in the expression of anxiety, including the CeA, basolateral amygdala, PFC, ventral hippocampus, and bed nucleus of the stria terminalis. 8 , 147 , 148 As with the findings observed in human subjects with AUD, the downregulation of CB 1 receptors appears to be an important attribute of mood affective disorders, at least within subcortical regions that are posited to interact more frequently with upstream hormonal regulators.…”

Section: Endocannabinoids and Withdrawal-related Anxietymentioning

confidence: 99%

Alcohol-Endocannabinoid Interactions: Implications for Addiction-Related Behavioral Processes

Serrano

Natividad

2022

ARCR

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“…The GABA receptors GABAA and GABAB are expressed on neurons and glial cells in the STN and their activation couples to a chloride channel or an inhibitory Gprotein, respectively. In addition, the endocannabinoid system is involved in descending pain modulation and is known to play an important role in modulating stress and anxiety in humans (23)(24)(25)(26) via activation of cannabinoid receptors (27,28). The diverse physiological and cellular effects of the endocannabinoid system are mediated by the G-protein-coupled receptors CB1 and CB2, which are expressed on axon terminals and glial cells in both the central and peripheral nervous systems (29).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Nociception in a Preclinical Episodic Migraine Model by Dietary Supplementation of Grape Seed Extract Involves Activation of Endocannabinoid Receptors

2022

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Migraine is associated with peripheral and central sensitization of the trigeminal system and dysfunction of descending pain modulation pathways. Recently, dietary inclusion of grape seed extract (GSE) was shown to inhibit mechanical nociception in a preclinical model of chronic temporomandibular joint disorder, a condition often comorbid with migraine, with the antinociceptive effect mediated, in part, by activation of 5-HT3/7 and GABAB receptors. This study further investigated the mechanisms by which GSE inhibits mechanical nociception in a preclinical model of episodic migraine. Hyperalgesic priming of female and male Sprague Dawley rats was induced by three consecutive daily two-hour episodes of restraint stress. Seven days after the final restraint stress, rats were exposed to pungent odors from an oil extract that contains the compound umbellulone, which stimulates CGRP release and induces migraine-like pain. Some animals received dietary supplementation of GSE in their drinking water beginning one week prior to restraint stress. Changes in mechanical sensitivity in the orofacial region and hindpaw were determined using von Frey filaments. To investigate the role of the endocannabinoid receptors in the effect of GSE, some animals were injected intracisternally with the CB1 antagonist AM 251 or the CB2 antagonist AM 630 prior to odor inhalation. Changes in CGRP expression in the spinal trigeminal nucleus (STN) in response to stress, odor and GSE supplementation were studied using immunohistochemistry. Exposure of stress-primed animals to the odor caused a significant increase in the average number of withdrawal responses to mechanical stimulation in both the orofacial region and hindpaw, and the effect was significantly suppressed by daily supplementation with GSE. The anti-nociceptive effect of GSE was inhibited by intracisternal administration of antagonists of CB1 and CB2 receptors. GSE supplementation inhibited odor-mediated stimulation of CGRP expression in the STN in sensitized animals. These results demonstrate that GSE supplementation inhibits trigeminal pain signaling in an injury-free model of migraine-like pain via activation of endocannabinoid receptors and repression of CGRP expression centrally. Hence, we propose that GSE may be beneficial as a complementary migraine therapeutic.

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Endocannabinoids, cannabinoids and the regulation of anxiety

Cited by 51 publications

References 367 publications

CB2 cannabinoid receptor expression is increased in 129S1/SvImJ mice: behavioral consequences

CB2 cannabinoid receptor expression is increased in 129S1/SvImJ mice: behavioral consequences

Alcohol-Endocannabinoid Interactions: Implications for Addiction-Related Behavioral Processes

Inhibition of Nociception in a Preclinical Episodic Migraine Model by Dietary Supplementation of Grape Seed Extract Involves Activation of Endocannabinoid Receptors

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