Loss of cannabinoid receptor binding and messenger RNA levels and cannabinoid agonist-stimulated [35s]guanylyl-5′-O-(thio)-triphosphate binding in the basal ganglia of aged rats

Romero, Julián; Berrendero, Fernando; Garcı́a-Gil, Lucı́a; Cruz, Pilar de la; Ramos, Jaime A.; Fernández‐Ruiz, Javier

doi:10.1016/s0306-4522(97)00552-6

Cited by 76 publications

(44 citation statements)

References 25 publications

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“…Abnormalities in cAMP signaling in depressive disorders have been reported. Dowlatshahi 34 In this study, we also observed (data not shown) reduced receptor density associated with increasing age in normal control subject, suggesting that receptor losses are related to the aging process. This observation is consistent with previous reports.…”

Section: Discussionsupporting

confidence: 69%

Upregulation of CB1 receptors and agonist-stimulated [35S]GTPγS binding in the prefrontal cortex of depressed suicide victims

Hungund

Vinod

Kassir³

et al. 2004

Mol Psychiatry

199

102

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Endogenous and exogenous cannabinoids (CBs) acting through the CB 1 receptors have been implicated in the regulation of several behavioral and neuroendocrine functions. Modulation of endocannabinoidergic system by ethanol in mouse brain, and the association of suicide and mood disorders with alcoholism suggest possible involvement of the cannabinoidergic system in the pathophysiology of depression and suicide. Therefore, the present study was undertaken to examine the levels of CB 1 receptors and mediated signaling in the dorsolateral prefrontal cortex (DLPFC) of subjects with major depression who had died by suicides (depressed suicides, DS).

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Section: Discussionsupporting

confidence: 69%

Upregulation of CB1 receptors and agonist-stimulated [35S]GTPγS binding in the prefrontal cortex of depressed suicide victims

Hungund

Vinod

Kassir³

et al. 2004

Mol Psychiatry

199

102

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“…(Sim et al, 1996;Romero et al, 1998). In the present study, no difference in basal [ 35 S]GTP␥S binding was found in any region between vehicle and treated brains.…”

contrasting

confidence: 62%

“…Chronic cannabinoid administration alters signaling at each level of the CB1 signal transduction cascade. Down-regulation (loss of binding sites) has been reported after chronic administration of ⌬ 9 -THC, as well as the synthetic cannabinoid agonist CP55,940 (Oviedo et al, 1993;Fan et al, 1996;Romero et al, 1998;Breivogel et al, 1999). Chronic ⌬ 9 -THC administration also produces desensitization (defined herein as a decrease in G protein activation) throughout the brain (Sim et al, 1996;Breivogel et al, 1999).…”

mentioning

confidence: 99%

Effect of Chronic Administration ofR-(+)-[2,3-Dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl)methanone Mesylate (WIN55,212-2) or Δ⁹-Tetrahydrocannabinol on Cannabinoid Receptor Adaptation in Mice

Sim‐Selley

Martin²

2002

J Pharmacol Exp Ther

120

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Agonist efficacy may influence the magnitude of neuroadaptation in response to chronic drug exposure. Chronic administration of either ⌬ 9 -tetrahydrocannabinol (THC), a partial agonist, or R-(ϩ)- [2,3-dihydro-5-methyl-3-[(morpholinyl)methyl] H]N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR141716A) binding was decreased in all brain regions in ⌬9 -THC-and WIN55,212-2-treated mice, with no difference between treatment groups. These results demonstrate that chronic treatment with either the partial agonist ⌬ 9 -THC or the full agonist WIN55,212-2 produces tolerance to cannabinoid-mediated behaviors, as well as cannabinoid receptor desensitization and downregulation. Furthermore, ⌬ 9 -THC produced greater desensitization than WIN55,212-2 in some regions, indicating that agonist efficacy is one determinant of cannabinoid receptor desensitization in brain.Chronic ⌬ 9 -THC administration produces tolerance (Carlini, 1968;McMillan et al., 1971), but the cellular mechanisms underlying cannabinoid tolerance have only recently been investigated, and the relationship between in vivo and in vitro adaptation has not been elucidated. CB1 receptors activate G proteins of the G i /G o subfamily (Howlett et al., 1986;Glass and Northup, 1999) and modulate adenylyl cyclase, potassium, and calcium channel conductance Mackie et al., 1995). Chronic cannabinoid administration alters signaling at each level of the CB1 signal transduction cascade. Down-regulation (loss of binding sites) has been reported after chronic administration of ⌬ 9 -THC, as well as the synthetic cannabinoid agonist CP55,940 (Oviedo et al

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“…The apparent affinity is similar to that observed in rat brain (Breivogel et al, 1997), albeit the density of binding sites (B max ) is much lower. Rather than a species trait, aging (Mailleux and Vanderhaeghen, 1992;Romero et al, 1998;Mato and Pazos, 2004) may account for the difference in density, given that our controls were nonpathological aged subjects. WIN55,212-2 is a mixed CB 1 /CB 2 cannabinoid receptor agonist that activates, with similar affinities, CB 1 and CB 2 receptors (Howlett et al, 2002) and may also interact with other, as yet uncharacterized, receptor subtypes (Breivogel et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Prevention of Alzheimer's Disease Pathology by Cannabinoids: Neuroprotection Mediated by Blockade of Microglial Activation

Ramírez¹,

Blázquez²,

Pulgar³

et al. 2005

J. Neurosci.

684

587

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Alzheimer's disease (AD) is characterized by enhanced ␤-amyloid peptide (␤A) deposition along with glial activation in senile plaques, selective neuronal loss, and cognitive deficits. Cannabinoids are neuroprotective agents against excitotoxicity in vitro and acute brain damage in vivo. This background prompted us to study the localization, expression, and function of cannabinoid receptors in AD and the possible protective role of cannabinoids after ␤A treatment, both in vivo and in vitro. Here, we show that senile plaques in AD patients express cannabinoid receptors CB 1 and CB 2 , together with markers of microglial activation, and that CB 1 -positive neurons, present in high numbers in control cases, are greatly reduced in areas of microglial activation. In pharmacological experiments, we found that G-protein coupling and CB 1 receptor protein expression are markedly decreased in AD brains. Additionally, in AD brains, protein nitration is increased, and, more specifically, CB 1 and CB 2 proteins show enhanced nitration. Intracerebroventricular administration of the synthetic cannabinoid WIN55,212-2 to rats prevent ␤A-induced microglial activation, cognitive impairment, and loss of neuronal markers. Cannabinoids (HU-210, WIN55,212-2, and JWH-133) block ␤A-induced activation of cultured microglial cells, as judged by mitochondrial activity, cell morphology, and tumor necrosis factor-␣ release; these effects are independent of the antioxidant action of cannabinoid compounds and are also exerted by a CB 2 -selective agonist. Moreover, cannabinoids abrogate microglia-mediated neurotoxicity after ␤A addition to rat cortical cocultures. Our results indicate that cannabinoid receptors are important in the pathology of AD and that cannabinoids succeed in preventing the neurodegenerative process occurring in the disease.

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Loss of cannabinoid receptor binding and messenger RNA levels and cannabinoid agonist-stimulated [35s]guanylyl-5′-O-(thio)-triphosphate binding in the basal ganglia of aged rats

Cited by 76 publications

References 25 publications

Upregulation of CB1 receptors and agonist-stimulated [35S]GTPγS binding in the prefrontal cortex of depressed suicide victims

Upregulation of CB1 receptors and agonist-stimulated [35S]GTPγS binding in the prefrontal cortex of depressed suicide victims

Effect of Chronic Administration ofR-(+)-[2,3-Dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl)methanone Mesylate (WIN55,212-2) or Δ⁹-Tetrahydrocannabinol on Cannabinoid Receptor Adaptation in Mice

Prevention of Alzheimer's Disease Pathology by Cannabinoids: Neuroprotection Mediated by Blockade of Microglial Activation

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Loss of cannabinoid receptor binding and messenger RNA levels and cannabinoid agonist-stimulated [35s]guanylyl-5′-O-(thio)-triphosphate binding in the basal ganglia of aged rats

Cited by 76 publications

References 25 publications

Upregulation of CB1 receptors and agonist-stimulated [35S]GTPγS binding in the prefrontal cortex of depressed suicide victims

Upregulation of CB1 receptors and agonist-stimulated [35S]GTPγS binding in the prefrontal cortex of depressed suicide victims

Effect of Chronic Administration ofR-(+)-[2,3-Dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl)methanone Mesylate (WIN55,212-2) or Δ9-Tetrahydrocannabinol on Cannabinoid Receptor Adaptation in Mice

Prevention of Alzheimer's Disease Pathology by Cannabinoids: Neuroprotection Mediated by Blockade of Microglial Activation

Contact Info

Product

Resources

About

Effect of Chronic Administration ofR-(+)-[2,3-Dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl)methanone Mesylate (WIN55,212-2) or Δ⁹-Tetrahydrocannabinol on Cannabinoid Receptor Adaptation in Mice