Anandamide hydrolysis: a new target for anti-anxiety drugs?

Gaetani, Silvana; Cuomo, V.; Piomelli, Daniele

doi:10.1016/j.molmed.2003.09.005

Cited by 94 publications

(70 citation statements)

References 47 publications

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“…Previous reports indicate that anandamide has a protective role in the response to environmental stressors (Hill et al, 2013;Hill et al, 2011;Kathuria et al, 2003;Patel and Hillard, 2006) and that stressful stimuli enhance anandamide mobilization in brain regions such as BLA and prefrontal cortex (Bortolato et al, 2006;Gaetani et al, 2003;Kathuria et al, 2003;Lutz, 2009;Marsicano et al, 2002;Hillard, 2006, 2008;Steiner et al, 2008). In the auditory fear-conditioning paradigm, administration of FAAH inhibitors into the BLA enhances fear extinction and impairs fear memory retrieval (Gunduz-Cinar et al, 2013;Marsicano and Lutz, 2006;Marsicano et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

“…Substantial evidence implicates the endocannabinoid system in the regulation of stress-coping responses (Bortolato et al, 2006;Gaetani et al, 2003;Hill et al, 2010;Kathuria et al, 2003;Lutz, 2009;Marsicano et al, 2002;Hillard, 2006, 2008;Steiner et al, 2008). Animal experiments suggest that activation of the endocannabinoid system contributes to stress-induced analgesia (Hohmann et al, 2005) and enhances stress-coping behaviors in mice and rats (Bortolato et al, 2007;Gobbi et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

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Endocannabinoid Modulation of Predator Stress-Induced Long-Term Anxiety in Rats

Lim

Igarashi

Jung

et al. 2015

Neuropsychopharmacol

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Individuals who experience life-threatening psychological trauma are at risk of developing a series of chronic neuropsychiatric pathologies that include generalized anxiety, depression, and drug addiction. The endocannabinoid system has been implicated in the modulation of these responses by regulating the activity of the amygdala and the hypothalamic-pituitary-adrenal axis. However, the relevance of this signaling complex to the long-term consequences of traumatic events is unclear. Here we use an animal model of predatory stress-induced anxiety-like behavior to investigate the role of the endocannabinoid system in the development of persistent anxiety states. Our main finding is that rats exposed to the fox pheromone 2,5-dihydro-2,4,5-trimethylthiazoline (TMT), a life-threatening stimulus for rodents, display a marked and selective increase in the mobilization of the endocannabinoid, 2-arachidonoyl-sn-glycerol (2-AG), in the amygdala. This effect lasts for at least 14 days after the stress has occurred. In addition, systemic or local pharmacological inhibition of monoacylglycerol lipase (MGL)-a lipid hydrolase that degrades 2-AG in presynaptic nerve terminals-elevates 2-AG levels and suppresses the anxiety-like behavior elicited by exposure to TMT. The results suggest that predator threat triggers long-term changes in 2-AG-mediated endocannabinoid signaling in the amygdala, and that pharmacological interventions targeting MGL might provide a therapeutic strategy for the treatment of chronic brain disorders initiated by trauma.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Endocannabinoid Modulation of Predator Stress-Induced Long-Term Anxiety in Rats

Lim

Igarashi

Jung

et al. 2015

Neuropsychopharmacol

Self Cite

View full text Add to dashboard Cite

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“…Relevant to our study is that our results are in agreement with in vivo studies demonstrating that the administration of AM404 or URB597, an inhibitor of the metabolic pathway of the endocannabinoid anandamide, do not mimic the full spectrum of pharmacological responses produced by classical CB1 receptor agonists (see Refs. [45,46] for a review). Hence, understanding in what circumstances endocannabinoids are released and activate histaminergic cells warrants further investigations and may provide interesting hints to develop new therapeutic strategies in the treatment, for instance, of food intake disorders.…”

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confidence: 99%

Histamine in the brain: Beyond sleep and memory

Passani¹,

Giannoni²,

Bucherelli

et al. 2007

Biochemical Pharmacology

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“…Similar results were obtained in the ultrasonic vocalization emission test, which measures the number of stress-induced vocalizations emitted by rat pups removed from their nest. These results suggest that inhibition of intracellular FAAH activity may offer an innovative target for the treatment of anxiety [126], which is also a feature of marijuana withdrawal [50,51,127]. Forebrain sites that might be implicated in such actions include the basolateral amygdala, the anterior cingulate cortex and the prefrontal cortex, all key elements of an 'emotion circuit' that contains high densities of CB1 receptors [18,19].…”

Section: Stress and Anxietymentioning

confidence: 97%

Cannabis and endocannabinoid modulators: Therapeutic promises and challenges

Grant

Cahn

2005

Clinical Neuroscience Research

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The discovery that botanical cannabinoids such as delta-9 tetrahydrocannabinol exert some of their effect through binding specific cannabinoid receptor sites has led to the discovery of an endocannabinoid signaling system, which in turn has spurred research into the mechanisms of action and addiction potential of cannabis on the one hand, while opening the possibility of developing novel therapeutic agents on the other. This paper reviews current understanding of CB1, CB2, and other possible cannabinoid receptors, their arachidonic acid derived ligands (e.g. anandamide; 2 arachidonoyl glycerol), and their possible physiological roles. CB1 is heavily represented in the central nervous system, but is found in other tissues as well; CB2 tends to be localized to immune cells. Activation of the endocannabinoid system can result in enhanced or dampened activity in various neural circuits depending on their own state of activation. This suggests that one function of the endocannabinoid system may be to maintain steady state. The therapeutic action of botanical cannabis or of synthetic molecules that are agonists, antagonists, or which may otherwise modify endocannabinoid metabolism and activity indicates they may have promise as neuroprotectants, and may be of value in the treatment of certain types of pain, epilepsy, spasticity, eating disorders, inflammation, and possibly blood pressure control.

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Anandamide hydrolysis: a new target for anti-anxiety drugs?

Cited by 94 publications

References 47 publications

Endocannabinoid Modulation of Predator Stress-Induced Long-Term Anxiety in Rats

Endocannabinoid Modulation of Predator Stress-Induced Long-Term Anxiety in Rats

Histamine in the brain: Beyond sleep and memory

Cannabis and endocannabinoid modulators: Therapeutic promises and challenges

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