Fatty acid amide hydrolase inhibitors produce rapid anti-anxiety responses through amygdala long-term depression in male rodents

Duan, Tingting; Gu, Ning; Wang, Ying; Feng, Wenquan; Zhu, Jie; Fang, Yiru; Shen, Yuan; Han, Jing; Zhang, Xia

doi:10.1503/jpn.160116

Cited by 33 publications

(19 citation statements)

References 59 publications

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“…This would be in agreement with other reports showing, for example, that AEA elicits place aversion in rats [169]. However, blockade of FAAH by URB597 has been shown to elicit anti-anxiety effects in rats [170][171][172][173][174][175]. Furthermore, to complicate this picture, AEA has been shown to be intravenously self-administered in squirrel monkeys, suggesting that under some circumstances it works as a behavioral reinforcer.…”

Section: The Endocannabinoid System In Brain Reward Processes Neurochsupporting

confidence: 92%

Brain activity of anandamide: a rewarding bliss?

et al. 2018

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Anandamide is a lipid mediator that acts as an endogenous ligand of CB1 receptors. These receptors are also the primary molecular target responsible for the pharmacological effects of Δ9-tetrahydrocannabinol, the psychoactive ingredient in Cannabis sativa. Several studies demonstrate that anandamide exerts an overall modulatory effect on the brain reward circuitry. Several reports suggest its involvement in the addiction-producing actions of other abused drugs, and it can also act as a behavioral reinforcer in animal models of drug abuse. Importantly, all these effects of anandamide appear to be potentiated by pharmacological inhibition of its metabolic degradation. Enhanced brain levels of anandamide after treatment with inhibitors of fatty acid amide hydrolase, the main enzyme responsible for its degradation, seem to affect the rewarding and reinforcing actions of many drugs of abuse. In this review, we will provide an overview from a preclinical perspective of the current state of knowledge regarding the behavioral pharmacology of anandamide, with a particular emphasis on its motivational/reinforcing properties. We will also discuss how modulation of anandamide levels through inhibition of enzymatic metabolic pathways could provide a basis for developing new pharmaco-therapeutic tools for the treatment of substance use disorders.

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Section: The Endocannabinoid System In Brain Reward Processes Neurochsupporting

confidence: 92%

Brain activity of anandamide: a rewarding bliss?

et al. 2018

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“…FAAH inhibitor PF3845 exerts rapid and long-lasting anxiolytic effects in mice exposed acutely and chronically to the stress hormone corticosterone [10]. This finding expands on the previous findings that the FAAH inhibitor URB597 produces anxiolytic effects 1 day after acute stress exposure [65] and that chronic injection of PF3845 exerts anxiolytic effects in chronic and mild stress-exposed animals [14].…”

Section: Role Of the Endocannabinoid System In Anxiety Therapysupporting

confidence: 82%

“…To understand this specificity in anxiety and depression, one needs an integrated view of the eCB-mediated control of relevant brain regions and their interregional connections. Within distinct cerebral regions, eCB signaling can differentially modulate the activity of multiple cell types (neuronal subtypes [6], astrocytes [9,10], and microglia [11]) and in turn execute context-related alterations in synaptic transmission. The present review examines the evidence for eCB influence in anxiety-and stress-related dysfunctions, such as depression, and the research on other neural circuits.…”

Section: Introductionmentioning

confidence: 99%

Integrating endocannabinoid signaling in the regulation of anxiety and depression

2018

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Brain endogenous cannabinoid (eCB) signaling seems to harmonize appropriate behavioral responses, which are essential for the organism's long-term viability and homeostasis. Dysregulation of eCB signaling contributes to negative emotional states and increased stress responses. An understanding of the underlying neural cell populations and neural circuit regulation will enable the development of therapeutic strategies to mitigate behavioral maladaptation and provide insight into the influence of eCB on the neural circuits involved in anxiety and depression. This review focuses on recent evidence that has added a new layer of complexity to the idea of targeting the eCB system for therapeutic benefits in neuropsychiatric disease and on the future research direction of neural circuit modulation.

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“…Consistent with the loss-of-function studies described above, pharmacological and genetic augmentation of eCB signaling via inhibition or deletion of 2-AG and AEA degradation decreases anxiety-like behaviors in a variety of preclinical models. For example, pharmacological inhibition of FAAH decreases unconditioned anxiety-like behaviors behavior in rats and mice in an array of behavioral tests including the light-dark box, the elevated-plus maze, the open-field test, and the novelty-induced suppression of feeding task (Duan et al, 2016;Hill et al, 2007;Kathuria et al, 2003;Kinsey et al, 2011;Moise et al, 2008;Morena et al, 2016a;Naidu et al, 2007;Patel and Hillard, 2006;Scherma et al, 2008). Moreover, genetic deletion of FAAH decreases anxiety-like behaviors via a CB1-dependent mechanism (Kathuria et al, 2003;Moreira et al, 2008).…”

Section: Endocannabinoids Cannabinoids and Anxietymentioning

confidence: 99%

“…Interestingly, mice lacking CB1 expression within serotonergic neurons also display increased anxiety and reduced sociability (Dubreucq et al, 2012;Haring et al, 2015), suggesting a role for eCBmediated modulation of monoaminergic circuits could also play a role. Studies performing site-specific manipulations of eCB signaling highlight the importance of eCB signaling in the mPFC and amygdala as important sites of action mediating these effects (Bluett et al, 2017;Duan et al, 2016;Gray et al, 2015;Morena et al, 2016a), which likely relates to the ability of eCB signaling in these structures to regulate excitatory and inhibitory neurotransmission (as discussed above). Defining the precise circuit mechanisms by eCB signaling and exogenous cannabinoids modulate anxietyrelated behaviors represents a critical area of further investigation.…”

Section: Endocannabinoids Cannabinoids and Anxietymentioning

confidence: 99%

Integrating Endocannabinoid Signaling and Cannabinoids into the Biology and Treatment of Posttraumatic Stress Disorder

Hill

Campolongo

Yehuda

et al. 2017

Neuropsychopharmacol.

185

129

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Exposure to stress is an undeniable, but in most cases surmountable, part of life. However, in certain individuals, exposure to severe or cumulative stressors can lead to an array of pathological conditions including posttraumatic stress disorder (PTSD), characterized by debilitating trauma-related intrusive thoughts, avoidance behaviors, hyperarousal, as well as depressed mood and anxiety. In the context of the rapidly changing political and legal landscape surrounding use of cannabis products in the USA, there has been a surge of public and research interest in the role of cannabinoids in the regulation of stress-related biological processes and in their potential therapeutic application for stress-related psychopathology. Here we review the current state of knowledge regarding the effects of cannabis and cannabinoids in PTSD and the preclinical and clinical literature on the effects of cannabinoids and endogenous cannabinoid signaling systems in the regulation of biological processes related to the pathogenesis of PTSD. Potential therapeutic implications of the reviewed literature are also discussed. Finally, we propose that a state of endocannabinoid deficiency could represent a stress susceptibility endophenotype predisposing to the development of trauma-related psychopathology and provide biologically plausible support for the self-medication hypotheses used to explain high rates of cannabis use in patients with trauma-related disorders.

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Fatty acid amide hydrolase inhibitors produce rapid anti-anxiety responses through amygdala long-term depression in male rodents

Cited by 33 publications

References 59 publications

Brain activity of anandamide: a rewarding bliss?

Brain activity of anandamide: a rewarding bliss?

Integrating endocannabinoid signaling in the regulation of anxiety and depression

Integrating Endocannabinoid Signaling and Cannabinoids into the Biology and Treatment of Posttraumatic Stress Disorder

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