Elevated circulating levels of anandamide after administration of the transport inhibitor, AM404

Giuffrida, Andrea; Fonseca, Fernando Rodrı́guez de; Nava, Felice; Loubet-Lescoulié, P; Piomelli, Daniele

doi:10.1016/s0014-2999(00)00786-x

Cited by 126 publications

(87 citation statements)

References 31 publications

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“…AM404, administered at a time and dose known to increase AEA content in plasma (Giuffrida et al, 2000), potentiated restraint-induced Fos expression within the CeA, although the magnitude of this increase was far less than that produced by direct CB 1 receptor agonists. In contrast, the FAAH inhibitor URB597, administered at a time and dose shown to increase brain AEA content and reduce FAAH activity (Kathuria et al, 2003), did not alter restraint-induced Fos expression within the BLA or CeA.…”

Section: Discussionmentioning

confidence: 90%

“…AM404 has low affinity for CB 1 receptors, but inhibits neuronal transport of the eCBs N-arachidonylethanolamine (AEA) and 2-arachidonylglycerol (2-AG) (Beltramo et al, 1997;Beltramo and Piomelli, 2000) and inhibits catabolism of AEA by fatty acid amide hydrolase (FAAH) (Jarrahian et al, 2000). AM404 (10 mg/kg) was administered 90 min prior to restraint stress to allow for the accumulation of extraneuronal eCBs (Giuffrida et al, 2000). We administered the irreversible FAAH inhibitor, URB597 (1 mg/kg), 90 min prior to restraint, a time point at which brain AEA content is elevated (Kathuria et al, 2003).…”

Section: Restraint Procedures and Tissue Preparationmentioning

confidence: 99%

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Synergistic Interactions between Cannabinoids and Environmental Stress in the Activation of the Central Amygdala

Patel

Cravatt

Hillard

2004

Neuropsychopharmacol

148

100

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Anxiety and panic are the most common adverse effects of cannabis intoxication; reactions potentiated by stress. Data suggest that cannabinoid (CB 1 ) receptor modulation of amygdalar activity contributes to these phenomena. Using Fos as a marker, we tested the hypothesis that environmental stress and CB 1 cannabinoid receptor activity interact in the regulation of amygdalar activation in male mice. Both 30 min of restraint and CB 1 receptor agonist treatment (D 9 -tetrahydrocannabinol (2.5 mg/kg) or CP55940 (0.3 mg/kg); by i.p. injection) produced barely detectable increases in Fos expression within the central amygdala (CeA). However, the combination of restraint and CB 1 agonist administration produced robust Fos induction within the CeA, indicating a synergistic interaction between environmental stress and CB 1 receptor activation. An inhibitor of endocannabinoid transport, AM404 (10 mg/kg), produced an additive interaction with restraint within the CeA. In contrast, fatty acid amide hydrolase (FAAH) inhibitor-treated mice (URB597, 1 mg/kg) and FAAH À/À mice did not exhibit any differences in amygdalar activation in response to restraint compared to control mice. In the basolateral (BLA) and medial amygdala, restraint stress produced a low level of Fos induction, which was unaffected by cannabinoid treatment. Interestingly, the CB 1 receptor antagonist SR141716 dose-dependently increased Fos expression in the BLA and CeA. These data suggest the CeA is an important neural substrate subserving the interactions between cannabinoids and environmental stress, and could be relevant to understanding the context-dependent emotional and affective changes induced by marijuana intoxication and the role of endocannabinoid signaling in the modulation of amygdalar activity.

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Section: Discussionmentioning

confidence: 90%

Section: Restraint Procedures and Tissue Preparationmentioning

confidence: 99%

Synergistic Interactions between Cannabinoids and Environmental Stress in the Activation of the Central Amygdala

Patel

Cravatt

Hillard

2004

Neuropsychopharmacol

148

100

View full text Add to dashboard Cite

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“…First, internalization of endocannabinoids is facilitated by the highly selective carrier-mediated transport system (Di Marzo et al, 1994;Beltramo et al, 1997;Hillard et al, 1997;Piomelli et al, 1999;Fegley et al, 2004). Inhibitors of the transport system have been shown to enhance the effects of exogenous cannabinoid ligands (Giuffrida et al, 2000;Fegley et al, 2004;Hájos et al, 2004). FAAH activity is the second step of endocannabinoid inactivation.…”

Section: Introductionmentioning

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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“…was administered to BD rats 15 min before NLX administration. AM404, which has been shown to increase AEA levels extracellularly (Giuffrida et al, 2000b), prevented naloxone-induced seizures in all BD rats tested (InfoStat, BD AM404-NLX 0/5 seizures vs. BD NLX 8/8 seizures, 2Î = 17.3232, df = 1, P b 0.001) (n = 5-8 per group) (Fig. 4C).…”

Section: Anandamide As An Endogenous Anticonvulsantmentioning

confidence: 78%

A role for endocannabinoids in viral-induced dyskinetic and convulsive phenomena

Solbrig

Adrian

Baratta

et al. 2005

Experimental Neurology

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Elevated circulating levels of anandamide after administration of the transport inhibitor, AM404

Cited by 126 publications

References 31 publications

Synergistic Interactions between Cannabinoids and Environmental Stress in the Activation of the Central Amygdala

Synergistic Interactions between Cannabinoids and Environmental Stress in the Activation of the Central Amygdala

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

A role for endocannabinoids in viral-induced dyskinetic and convulsive phenomena

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