Evaluation of the cannabinoid CB2 receptor-selective antagonist, SR144528: further evidence for cannabinoid CB2 receptor absence in the rat central nervous system

Griffin, Graeme; Wray, Emma J; Qing, Tao; McAllister, Sean D.; Rorrer, William K; Aung, MieMie; Martin, Billy R.; Abood, Mary E.

doi:10.1016/s0014-2999(99)00402-1

Cited by 137 publications

(94 citation statements)

References 14 publications

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“…A second type of cannabinoid receptor, the CB 2 class, is only present in the periphery (Griffin et al, 1999;Palmer et al, 2002). The relationship between CB 1 receptors and prosurvival FAK and ERK signaling seems to support the maintenance of hippocampal neurons (Derkinderen et al, 1998;Karanian et al, 2005) and may explain the protective properties linked to the CB 1 receptors (Nagayama et al, 1999;Panikashvili et al, 2001;Maccarrone et al, 2003;Marsicano et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Dual Modulation of Endocannabinoid Transport and Fatty Acid Amide Hydrolase Protects against Excitotoxicity

Karanian¹,

Brown²,

Makriyannis³

et al. 2005

J. Neurosci.

114

109

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The endocannabinoid system has been suggested to elicit signals that defend against several disease states including excitotoxic brain damage. Besides direct activation with CB 1 receptor agonists, cannabinergic signaling can be modulated through inhibition of endocannabinoid transport and fatty acid amide hydrolase (FAAH), two mechanisms of endocannabinoid inactivation. To test whether the transporter and FAAH can be targeted pharmacologically to modulate survival/repair responses, the transport inhibitor N-(4-hydroxyphenyl)-arachidonamide (AM404) and the FAAH inhibitor palmitylsulfonyl fluoride (AM374) were assessed for protection against excitotoxicity in vitro and in vivo. AM374 and AM404 both enhanced mitogen-activated protein kinase (MAPK) activation in cultured hippocampal slices. Interestingly, combining the distinct inhibitors produced additive effects on CB 1 signaling and associated neuroprotection. After an excitotoxic insult in the slices, infusing the AM374/AM404 combination protected against cytoskeletal damage and synaptic decline, and the protection was similar to that produced by the stable CB 1 agonist AM356 (R-methanandamide). AM374/ AM404 and the agonist also elicited cytoskeletal and synaptic protection in vivo when coinjected with excitotoxin into the dorsal hippocampus. Correspondingly, potentiating endocannabinoid responses with the AM374/AM404 combination prevented behavioral alterations and memory impairment that are characteristic of excitotoxic damage. The protective effects mediated by AM374/AM404 were (1) evident 7 d after insult, (2) correlated with the preservation of CB 1 -linked MAPK signaling, and (3) were blocked by a selective CB 1 antagonist. These results indicate that dual modulation of the endocannabinoid system with AM374/AM404 elicits neuroprotection through the CB 1 receptor. The transporter and FAAH are modulatory sites that may be exploited to enhance cannabinergic signaling for therapeutic purposes.

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Section: Discussionmentioning

confidence: 99%

Dual Modulation of Endocannabinoid Transport and Fatty Acid Amide Hydrolase Protects against Excitotoxicity

Karanian¹,

Brown²,

Makriyannis³

et al. 2005

J. Neurosci.

114

109

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“…Cells in healthy brain do not express CB 2 cannabinoid receptors (Munro et al, 1993;Griffin et al, 1999;Zimmer et al, 1999;Buckley et al, 2000). However, immune cells such as microglial cells, the macrophages of the brain, frequently alter levels of gene expression and express new gene products when stimulated with antigens and other bioactive substances.…”

Section: Glial Cells Express Cannabinoid Receptorsmentioning

confidence: 99%

Cannabinoids and neuroinflammation

Walter

Stella

2004

British J Pharmacology

305

215

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Growing evidence suggests that a major physiological function of the cannabinoid signaling system is to modulate neuroinflammation. This review discusses the anti-inflammatory properties of cannabinoid compounds at molecular, cellular and whole animal levels, first by examining the evidence for anti-inflammatory effects of cannabinoids obtained using in vivo animal models of clinical neuroinflammatory conditions, specifically rodent models of multiple sclerosis, and second by describing the endogenous cannabinoid (endocannabinoid) system components in immune cells. Our aim is to identify immune functions modulated by cannabinoids that could account for their antiinflammatory effects in these animal models.

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“…When CB 2 Rs were first cloned, in situ hybridization (ISH) failed to detect CB 2 mRNA in brain (1). Similarly, Northern blot and polymerase chain reaction (PCR) assays failed to detect CB 2 mRNA in brain (2)(3)(4)(5). Therefore, CB 2 Rs were considered "peripheral cannabinoid receptors" (1,6).…”

mentioning

confidence: 99%

Cannabinoid CB ₂ receptors modulate midbrain dopamine neuronal activity and dopamine-related behavior in mice

Zhang

Gao

Liu

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

310

353

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Cannabinoid CB 2 receptors (CB 2 Rs) have been recently reported to modulate brain dopamine (DA)-related behaviors; however, the cellular mechanisms underlying these actions are unclear. Here we report that CB 2 Rs are expressed in ventral tegmental area (VTA) DA neurons and functionally modulate DA neuronal excitability and DA-related behavior. In situ hybridization and immunohistochemical assays detected CB 2 mRNA and CB 2 R immunostaining in VTA DA neurons. Electrophysiological studies demonstrated that activation of CB 2 Rs by JWH133 or other CB 2 R agonists inhibited VTA DA neuronal firing in vivo and ex vivo, whereas microinjections of JWH133 into the VTA inhibited cocaine self-administration. Importantly, all of the above findings observed in WT or CB 1 −/− mice are blocked by CB 2 R antagonist and absent in CB 2 −/− mice. These data suggest that CB 2 R-mediated reduction of VTA DA neuronal activity may underlie JWH133's modulation of DA-regulated behaviors.T he presence of functional cannabinoid CB 2 receptors (CB 2 Rs) in the brain has been controversial. When CB 2 Rs were first cloned, in situ hybridization (ISH) failed to detect CB 2 mRNA in brain (1). Similarly, Northern blot and polymerase chain reaction (PCR) assays failed to detect CB 2 mRNA in brain (2-5). Therefore, CB 2 Rs were considered "peripheral cannabinoid receptors" (1, 6).In contrast, other studies using ISH and radioligand binding assays detected CB 2 mRNA and receptor binding in rat retina (7), mouse cerebral cortex (8), and hippocampus and striatum of nonhuman primates (9). More recent studies using RT-PCR also detected CB 2 mRNA in the cortex, striatum, hippocampus, amygdala, and brainstem (9-14). Immunoblot and immunohistochemistry (IHC) assays detected CB 2 R immunoreactivity or immunostaining in various brain regions (13,(15)(16)(17)(18)(19)(20). The specificities of the detected CB 2 R protein and CB 2 -mRNA remain questionable, however, owing to a lack of controls using CB 1 −/− and CB 2 −/− mice in most previous studies (21). A currently accepted view is that brain CB 2 Rs are expressed predominantly in activated microglia during neuroinflammation, whereas brain neurons, except for a very small number in the brainstem, lack CB 2 R expression (21).On the other hand, we recently reported that brain CB 2 Rs modulate cocaine self-administration and cocaine-induced increases in locomotion and extracellular dopamine (DA) in the nucleus accumbens in mice (22). This finding is supported by recent studies demonstrating that systemic administration of the CB 2 R agonist O-1966 inhibited cocaine-induced conditioned place preference in WT mice, but not in CB 2 −/− mice (23), and that increased CB 2 R expression in mouse brain attenuates cocaine self-administration and cocaine-enhanced locomotion (19). In addition, brain CB 2 Rs may be involved in several DA-related CNS disorders, such as Parkinson's disease (24), schizophrenia (25), anxiety (26), and depression (27). The cellular mechanisms underlying CB 2 R modulation of DA-related behav...

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Evaluation of the cannabinoid CB2 receptor-selective antagonist, SR144528: further evidence for cannabinoid CB2 receptor absence in the rat central nervous system

Cited by 137 publications

References 14 publications

Dual Modulation of Endocannabinoid Transport and Fatty Acid Amide Hydrolase Protects against Excitotoxicity

Dual Modulation of Endocannabinoid Transport and Fatty Acid Amide Hydrolase Protects against Excitotoxicity

Cannabinoids and neuroinflammation

Cannabinoid CB ₂ receptors modulate midbrain dopamine neuronal activity and dopamine-related behavior in mice

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Evaluation of the cannabinoid CB2 receptor-selective antagonist, SR144528: further evidence for cannabinoid CB2 receptor absence in the rat central nervous system

Cited by 137 publications

References 14 publications

Dual Modulation of Endocannabinoid Transport and Fatty Acid Amide Hydrolase Protects against Excitotoxicity

Dual Modulation of Endocannabinoid Transport and Fatty Acid Amide Hydrolase Protects against Excitotoxicity

Cannabinoids and neuroinflammation

Cannabinoid CB 2 receptors modulate midbrain dopamine neuronal activity and dopamine-related behavior in mice

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Product

Resources

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Cannabinoid CB ₂ receptors modulate midbrain dopamine neuronal activity and dopamine-related behavior in mice