Age-dependent plasticity in endocannabinoid modulation of pain processing through postnatal development

Kwok, Charlie H.T.; Devonshire, Ian M.; Imraish, Amer; Greenspon, Charles M.; Lockwood, Stevie; Fielden, Catherine; Cooper, Andrew H.; Woodhams, Stephen G; Sarmad, Sarir; Ortori, Catharine A.; Kendall, David A.; Bennett, Andrew J.; Chapman, Victoria; Hathway, Gareth J.

doi:10.1097/j.pain.0000000000001027

Cited by 13 publications

(7 citation statements)

References 59 publications

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“…In humans, the expression of NAPE‐PLD mRNA in the midbrain was highest in infants compared with both preterm and full‐term neonates. Altogether, these findings suggest that the expression of AEA increases within the brainstem nuclei of mammals during postnatal development (Kwok et al, 2017).…”

Section: Developmental Facets Of the Ecsmentioning

confidence: 91%

“…However, a complex picture arises for ECS function as endocannabinoid signaling is inhibited by a fatty acid amide hydrolase (FAAH) responsible for AEA hydrolysis and by monoacylglycerol lipase (MAGL) responsible for the hydrolysis of 2‐AG. In addition, another degradative pathway, for both AEA and 2‐AG, that involves cyclooxygenase‐2 (COX‐2) has been proposed (Battista, Tommaso, Bari, & Maccarrone, 2012; Di Marzo, Bifulco, & De Petrocellis, 2004; Kwok et al, 2017; Piomelli, 2003; see reviews: Jutras‐Aswad, DiNieri, Harkany, & Hurd, 2009; Katona & Freund, 2012; Lee, Hill, & Lee, 2016).…”

Section: The Endocannabinoid Systemmentioning

confidence: 99%

“…The role of the ECS signaling in neurodevelopment and brain maturation continues after birth (Fride, 2004; Klein et al, 2011). In animal models, AEA content has been observed to gradually increase during early postnatal stages, reaching its maximum in the adolescent brain (Harkany et al, 2007; Kwok et al, 2017). In particular, in the rat brain, CB1 receptors reach maximal densities during adolescence and later drop to adult expression levels in the dorsal striatum (Belue et al, 1995; de Fonseca et al, 1993).…”

Section: Developmental Facets Of the Ecsmentioning

confidence: 99%

“…Recent studies show that tissue levels of anandamide and 2‐AG within the periaqueductal grey and rostral ventromedial medulla are developmentally dependent. In human brainstem, age‐related alterations in the expression of key enzymes and receptors involved in ECS function using PCR and in situ hybridization have been shown (Kwok et al, 2017). Liquid chromatography–mass spectrometry analysis further showed augmentation in the levels of AEA in both the periaqueductal grey and rostral ventromedial medulla.…”

Section: Developmental Facets Of the Ecsmentioning

confidence: 99%

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Early life stress and development of the endocannabinoid system: A bidirectional process in programming future coping

Ferber

Trezza

Weller

2019

Developmental Psychobiology

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The endocannabinoid system (ECS) critically regulates stress responsivity and emotional behavior throughout development. It regulates anxiety‐like behaviors in humans and animal models. In addition, it is sensitive to early life stress at the gene expression level in a sex‐dependent and region‐dependent manner, and these changes are already evident in the adolescent brain. The ECS modulates the neuroendocrine and behavioral effects of stress, and is also capable of being affected by stress exposure itself. Early life stress interferes with the development of corticolimbic circuits, a major location of endocannabinoid receptors, and increases vulnerability to adult psychopathology. Early life stress alters the ontogeny of the ECS, resulting in a sustained deficit in its function, particularly within the hippocampus. Specifically, exposure to early stress results in bidirectional changes in anandamide and 2‐AG tissue levels within the amygdala and hippocampus and reduces hippocampal endocannabinoid function at puberty. CB1 receptor densities across all brain regions are downregulated later in life following exposure to early life stress. Manipulations affecting the glucocorticoid and the endocannabinoid systems persistently adjust individual emotional responses and synaptic plasticity. This review aims to show the bidirectional trajectories of endocannabinoid modulation of emotionality in reaction to early life stress.

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Section: Developmental Facets Of the Ecsmentioning

confidence: 91%

Section: The Endocannabinoid Systemmentioning

confidence: 99%

Section: Developmental Facets Of the Ecsmentioning

confidence: 99%

Section: Developmental Facets Of the Ecsmentioning

confidence: 99%

See 2 more Smart Citations

Early life stress and development of the endocannabinoid system: A bidirectional process in programming future coping

Ferber

Trezza

Weller

2019

Developmental Psychobiology

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“…Rats in that study were exposed to intermittent alcohol vapor or to the chamber without alcohol vapor for six weeks, thus they were older at the time of euthanasia than animals in the current study. This is important to note because age-related alterations in the expression of eCBs, key enzymes and receptors involved in eCBs function have been reported in both rodent and human brains ( Kwok et al, 2017 ).…”

Section: Discussionmentioning

confidence: 97%

Amygdalar endocannabinoids are affected by predator odor stress in a sex-specific manner and modulate acoustic startle reactivity in female rats

Albrechet‐Souza

Nastase

Hill

et al. 2021

Neurobiology of Stress

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Understanding sex differences in behavioral and molecular effects of stress has important implications for understanding the vulnerability to chronic psychiatric disorders associated with stress response circuitry. The amygdala is critical for emotional learning and generating behavioral responses to stressful stimuli, and preclinical studies indicate that amygdalar endocannabinoid (eCB) signaling regulates emotional states. This study measured eCB contents in the basolateral (BLA) and central (CeA) amygdala of male and female rats exposed to predator odor stress (bobcat urine) and tested for contextual avoidance 24 h later. Stressed females had lower levels of 2-arachidonoyl glycerol (2-AG) in the BLA and higher levels of anandamide (AEA) in the CeA, while exposure to bobcat urine did not affect amygdalar eCB contents in males. We previously reported that female rats exposed to bobcat urine exhibit blunted acoustic startle reactivity (ASR) 48 h after predator odor stress. Therefore, we tested the hypothesis that intra-BLA injection of a diacylglycerol lipase (DAGL) inhibitor (which would be expected to reduce 2-AG levels in BLA) and intra-CeA injection of a fatty acid amide hydrolase (FAAH) inhibitor (which would be expected to increase AEA levels in CeA) would mimic previously observed predator odor stress-induced reductions in ASR. Contrary to our hypothesis, microinjections of either the DAGL inhibitor DO34 into the BLA or the FAAH inhibitor URB597 into the CeA significantly increased ASR in females compared to vehicle-treated rats. These findings describe sex-specific effects of predator odor stress on amygdalar eCBs, and new roles for amygdalar eCBs in regulating behavior in females.

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Animal and Environmental Factors That Influence Reproducibility

Sánchez-Morgado

Brønstad

Pritchett-Corning

2021

Experimental Design and Reproducibility in Preclinical Animal Studies

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Age-dependent plasticity in endocannabinoid modulation of pain processing through postnatal development

Abstract: Supplemental Digital Content is Available in the Text.Endocannabinoid signalling within brainstem centres that control top-down pain control changes significantly in early life in both rodents and humans.

Cited by 13 publications

References 59 publications

Early life stress and development of the endocannabinoid system: A bidirectional process in programming future coping

Early life stress and development of the endocannabinoid system: A bidirectional process in programming future coping

Amygdalar endocannabinoids are affected by predator odor stress in a sex-specific manner and modulate acoustic startle reactivity in female rats

Animal and Environmental Factors That Influence Reproducibility

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