Endocannabinoid CB1 receptor activation upon global ischemia adversely impact recovery of reward and stress signaling molecules, neuronal survival and behavioral impulsivity

Knowles, Megan Dunbar; Tremblaye, Patricia B. de la; Azogu, Idu; Plamondon, Hélène

doi:10.1016/j.pnpbp.2015.10.010

Cited by 27 publications

(25 citation statements)

References 84 publications

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“…In agreement, Knowles et al. (2016) have shown that AM251, attenuated emotional changes induced by global ischemia in rats, indicating a prominent role of CB 1 receptors on the modulation of anxiety‐like behaviors induced by cerebral ischemia in rodents (Knowles et al., 2016). The mechanisms by which CB 2 receptors are involved in BCCAO‐induced anxiety is still unclear.…”

Section: Discussionsupporting

confidence: 62%

“…Similar mechanisms might have been involved in this study with BCCAO mice since AM251 and AM630 receptor antagonists blocked the anxiolytic-like effect of CBD. In agreement, Knowles et al (2016) have shown that AM251, attenuated emotional changes induced by global ischemia in rats, indicating a prominent role of CB 1 receptors on the modulation of anxiety-like behaviors induced by cerebral ischemia in rodents (Knowles et al, 2016). The mechanisms by which CB 2 receptors are involved in BCCAO-induced anxiety is still F I G U R E 5 Effects of cannabidiol (CBD) and CB1, CB2, 5-HT1A, and PPAR-γ receptor antagonists in BCCAO mice tested in the forced swim test (FST).…”

Section: Discussionmentioning

confidence: 68%

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Differential contribution of CB1, CB2, 5‐HT1A, and PPAR‐γ receptors to cannabidiol effects on ischemia‐induced emotional and cognitive impairments

Mori

Meyer

Silva

et al. 2021

Eur J of Neuroscience

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An ever-increasing body of preclinical studies has shown the multifaceted neuroprotective profile of cannabidiol (CBD) against impairments caused by cerebral ischemia. In this study, we have explored the neuropharmacological mechanisms of CBD action and its impact on functional recovery using a model of transient global cerebral ischemia in mice. C57BL/6J mice were subjected to bilateral common carotid artery occlusion (BCCAO) for 20 min and received vehicle or CBD (10 mg/Kg) 0.5 hr before and 3, 24, and 48 hr after reperfusion. To investigate the neuropharmacological mechanisms of CBD, the animals were injected with CB 1 (AM251, 1 mg/kg), CB 2 (AM630, 1 mg/kg), 5-HT 1A (WAY-100635, 10 mg/kg), or PPAR-γ (GW9662, 3 mg/kg) receptor antagonists 0.5 hr prior to each injection of CBD. The animals were evaluated using a multi-task testing battery that included the open field, elevated zero maze, Y-maze (YM), and forced swim test. CBD prevented anxietylike behavior, memory impairments, and despair-like behaviors induced by BCCAO in mice. The anxiolytic-like effects of CBD in BCCAO mice were attenuated by CB 1 , CB 2 , 5-HT 1A , and PPAR-γ receptor antagonists. In the YM, both CBD and the CB 1 receptor antagonist AM251 increased the exploration of the novel arm in ischemic animals, indicating beneficial effects of these treatments in the spatial memory performance. Together, these findings indicate the involvement of CB 1 , CB 2 , 5-HT 1A, and PPAR-γ receptors in the functional recovery induced by CBD in BCCAO mice.

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Section: Discussionsupporting

confidence: 62%

Section: Discussionmentioning

confidence: 68%

Differential contribution of CB1, CB2, 5‐HT1A, and PPAR‐γ receptors to cannabidiol effects on ischemia‐induced emotional and cognitive impairments

Mori

Meyer

Silva

et al. 2021

Eur J of Neuroscience

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“…CB1 receptor blocker AM251 has been known to be protective against transient focal cerebral ischemia [12]. Dunbar et al recently reported attenuation of CA1 injury by AM251 [19]. Interestingly, using CB1 receptor agonist could also capable of decreasing hippocampal neuronal loss following transient GCI and reducing the infarct volume after focal ischemia induced by middle cerebral artery occlusion [12].…”

Section: Discussionmentioning

confidence: 99%

Combined Neuroprotective Action of JWH-015 and AM251 in the CA1 Hippocampal Area of Transient Global Cerebral Ischemia

Shiasi¹,

Mortezaee²,

Abolhassani³

et al. 2017

Preprint

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Transient global cerebral ischemia (TGCI) induces by bilateral common carotid artery occlusion (BCCAO), and it mediates neuronal cell death of the CA1 hippocampal area. AM251 is a cannabinoid receptors type 1 (CB1) blocker that has been known to be protective against transient focal cerebral ischemia. JWH-015 is a selective agonist of CB2 and activator of CB1 that is involved in promotion of neuronal recovery and survival. The role of combined application of JWH-015 with AM251 in the rat model of GCI has been surveyed in this study. Male Wistar rats underwent 20 min of ischemia followed by reperfusion. Then, 1 mg/kg JWH-015 and 2 mg/kg AM251 were administered through caudal vein. The groups were control, sham, ischemia, vehicle, AM251, JWH-015 and AM251 + JWH-015. Animals were sacrificed at 14 days after reperfusion. The AM251 + JWH-015 group showed a significant increase in the protein expressions of AKT1, Bad 14-3-3, Bcl-2 and Bcl-XL, but it showed a considerable decrease in the protein expressions of Bad and JNK1/2 (p ≤ 0.05 vs. AM251, and JWH-015 groups). The AM251 + JWH-015 group had a significant higher number of alive cells and lower number of TUNEL-positive cells in the CA1 hippocampal area, and it also had a considerable improvement of spatial memory (p ≤ 0.05 vs. AM251, and JWH-015 groups). The results of this study showed that combined application of AM251 and JWH-015 could be neuroprotective against detrimental effects of ischemia probably via suppression of neuronal apoptosis and maintenance of their survival.

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“…However, there is some ambiguity over CB1R’s neuroprotective role in cerebral ischemia [ 417 ]. In two separate studies, CB1R antagonists SR141716A and AM251 were shown to have beneficial effects in attenuating neuronal damage caused by cerebral ischemia [ 418 , 419 ]. Interestingly, CB2R agonists have also been shown to mitigate inflammatory states and promote neurogenesis in post stroke and post intracerebral hemorrhage [ 420 , 421 ].…”

Section: Biological Role Of the Cannabinoid Receptorsmentioning

confidence: 99%

Cannabinoid Receptors: An Update on Cell Signaling, Pathophysiological Roles and Therapeutic Opportunities in Neurological, Cardiovascular, and Inflammatory Diseases

Haspula

Clark

2020

IJMS

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The identification of the human cannabinoid receptors and their roles in health and disease, has been one of the most significant biochemical and pharmacological advancements to have occurred in the past few decades. In spite of the major strides made in furthering endocannabinoid research, therapeutic exploitation of the endocannabinoid system has often been a challenging task. An impaired endocannabinoid tone often manifests as changes in expression and/or functions of type 1 and/or type 2 cannabinoid receptors. It becomes important to understand how alterations in cannabinoid receptor cellular signaling can lead to disruptions in major physiological and biological functions, as they are often associated with the pathogenesis of several neurological, cardiovascular, metabolic, and inflammatory diseases. This review focusses mostly on the pathophysiological roles of type 1 and type 2 cannabinoid receptors, and it attempts to integrate both cellular and physiological functions of the cannabinoid receptors. Apart from an updated review of pre-clinical and clinical studies, the adequacy/inadequacy of cannabinoid-based therapeutics in various pathological conditions is also highlighted. Finally, alternative strategies to modulate endocannabinoid tone, and future directions are also emphasized.

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Endocannabinoid CB1 receptor activation upon global ischemia adversely impact recovery of reward and stress signaling molecules, neuronal survival and behavioral impulsivity

Cited by 27 publications

References 84 publications

Differential contribution of CB1, CB2, 5‐HT1A, and PPAR‐γ receptors to cannabidiol effects on ischemia‐induced emotional and cognitive impairments

Differential contribution of CB1, CB2, 5‐HT1A, and PPAR‐γ receptors to cannabidiol effects on ischemia‐induced emotional and cognitive impairments

Combined Neuroprotective Action of JWH-015 and AM251 in the CA1 Hippocampal Area of Transient Global Cerebral Ischemia

Cannabinoid Receptors: An Update on Cell Signaling, Pathophysiological Roles and Therapeutic Opportunities in Neurological, Cardiovascular, and Inflammatory Diseases

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