Preservation of Striatal Cannabinoid CB1 Receptor Function Correlates with the Antianxiety Effects of Fatty Acid Amide Hydrolase Inhibition

Rossi, Silvia; Chiara, Valentina De; Musella, Alessandra; Sacchetti, Lucia; Cantarella, Cristina; Castelli, Maura; Cavasinni, Francesca; Motta, Caterina; Studer, Valeria; Bernardi, Giorgio; Cravatt, Benjamin F.; Maccarrone, Mauro; Usiello, Alessandro; Centonze, Diego

doi:10.1124/mol.110.064196

Cited by 76 publications

(53 citation statements)

References 56 publications

(91 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consistent with this model, we have demonstrated that stress-induced release of CRH rapidly triggers FAAH activity in the BLA to reduce AEA signaling, which in turn promotes the generation of anxiety (Gray et al, 2015). Importantly, central AEA levels are negatively correlated with anxiety-like behaviors , and elevating AEA signaling can effectively curb anxiety induced by both acute and chronic stress Campos et al, 2010;Hill et al, 2013b;Lomazzo et al, 2015;Rossi et al, 2010). As such, it has been proposed that AEA may function as a mediator of 'emotional homeostasis' (Haller et al, 2013;Marco and Viveros, 2009), functioning to keep anxiety at bay in resting conditions, from which disruption of this signal by stress could contribute to the generation of an anxious state (Gunduz-Cinar et al, 2013a).…”

Section: Functional Role Of Ecb Signaling In the Neurobiological Effesupporting

confidence: 69%

“…With the exception of the PFC, chronic stress is associated with a downregulation of CB1 receptor expression. Using electrophysiology, mRNA, protein, and radioligand binding, downregulation of the CB1 receptor has been found in the hippocampus (Hill et al, 2005b(Hill et al, , 2008bHu et al, 2011;Lee and Hill, 2013;Reich et al, 2009), hypothalamus (Hill et al, 2008b;Wamsteeker Cusulin et al, 2014;Wamsteeker et al, 2010), striatum (Hill et al, 2008b;Rossi et al, 2008Rossi et al, , 2010Wang et al, 2010), and dorsal root ganglion (Hong et al, 2011) following exposure to an array of both chronic homotypic and heterotypic stressors. The amygdala appears to be somewhat resistant to these effects as many reports have demonstrated no effect of chronic stress on CB1 expression using radioligand binding (Hill et al, 2008b;Lee and Hill, 2013); at the electrophysiological level, however, chronic homotypic stress has been shown to desensitize CB1 receptors in the BLA, at least on GABAergic terminals (Patel et al, 2009).…”

Section: Effects Of Acute and Chronic Stress On Cb1 Receptorsmentioning

confidence: 99%

See 1 more Smart Citation

Neurobiological Interactions Between Stress and the Endocannabinoid System

Morena

Patel

Bains

et al. 2015

Neuropsychopharmacol

510

496

View full text Add to dashboard Cite

Stress affects a constellation of physiological systems in the body and evokes a rapid shift in many neurobehavioral processes. A growing body of work indicates that the endocannabinoid (eCB) system is an integral regulator of the stress response. In the current review, we discuss the evidence to date that demonstrates stress-induced regulation of eCB signaling and the consequential role changes in eCB signaling have with respect to many of the effects of stress. Across a wide array of stress paradigms, studies have generally shown that stress evokes bidirectional changes in the two eCB molecules, anandamide (AEA) and 2-arachidonoyl glycerol (2-AG), with stress exposure reducing AEA levels and increasing 2-AG levels. Additionally, in almost every brain region examined, exposure to chronic stress reliably causes a downregulation or loss of cannabinoid type 1 (CB1) receptors. With respect to the functional role of changes in eCB signaling during stress, studies have demonstrated that the decline in AEA appears to contribute to the manifestation of the stress response, including activation of the hypothalamic-pituitary-adrenal (HPA) axis and increases in anxiety behavior, while the increased 2-AG signaling contributes to termination and adaptation of the HPA axis, as well as potentially contributing to changes in pain perception, memory and synaptic plasticity. More so, translational studies have shown that eCB signaling in humans regulates many of the same domains and appears to be a critical component of stress regulation, and impairments in this system may be involved in the vulnerability to stress-related psychiatric conditions, such as depression and posttraumatic stress disorder. Collectively, these data create a compelling argument that eCB signaling is an important regulatory system in the brain that largely functions to buffer against many of the effects of stress and that dynamic changes in this system contribute to different aspects of the stress response.

show abstract

Section: Functional Role Of Ecb Signaling In the Neurobiological Effesupporting

confidence: 69%

Section: Effects Of Acute and Chronic Stress On Cb1 Receptorsmentioning

confidence: 99%

Neurobiological Interactions Between Stress and the Endocannabinoid System

Morena

Patel

Bains

et al. 2015

Neuropsychopharmacol

510

496

View full text Add to dashboard Cite

show abstract

“…The ECS has important roles in both psychiatric disorders (Lutz, 2009;Hill and Patel, 2013) and pain states (Kinsey et al, 2009Piomelli et al, 2006;Piomelli and Sasso, 2014). The anxiolytic and analgesic properties of inhibitors of FAAH and MAGL have been extensively described (Kathuria et al, 2003;Jhaveri et al, 2006;Rossi et al, 2010;Sciolino et al, 2011;Ghosh et al, 2013;Kinsey et al, 2013). Therefore, targeting the ECS may represent a therapeutic strategy, particularly for the treatment of chronic pain associated with emotional imbalance.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Potential of Inhibitors of Endocannabinoid Degradation for the Treatment of Stress-Related Hyperalgesia in an Animal Model of Chronic Pain

Lomazzo

Bîndilă

Remmers

et al. 2014

Neuropsychopharmacol

125

View full text Add to dashboard Cite

The occurrence of chronic stress, depression, and anxiety can increase nociception in humans and may facilitate the transition from localized to chronic widespread pain. The mechanisms underlying chronic widespread pain are still unknown, hindering the development of effective pharmacological therapies. Here, we exposed C57BL/6J mice to chronic unpredictable stress (CUS) to investigate how persistent stress affects nociception. Next, mice were treated with multiple intramuscular nerve growth factor (NGF) injections, which induced chronic widespread nociception. Thus, combination of CUS and NGF served as a model where psychophysiological impairment coexists with long-lasting hyperalgesia. We found that CUS increased anxiety-and depression-like behavior and enhanced basal nociception in mice. When co-applied with repeated NGF injections, CUS elicited a sustained long-lasting widespread hyperalgesia. In order to evaluate a potential therapeutic strategy for the treatment of chronic pain associated with stress, we hypothesized that the endocannabinoid system (ECS) may represent a target signaling system. We found that URB597, an inhibitor of the anandamidedegrading enzyme fatty acid amide hydrolase (FAAH), and JZL184, an inhibitor of the 2-arachidonoyl glycerol-degrading enzyme monoacylglycerol lipase (MAGL), increased eCB levels in the brain and periphery and were both effective in reducing CUS-induced anxiety measured by the light-dark test and CUS-induced thermal hyperalgesia. Remarkably, the long-lasting widespread hyperalgesia induced by combining CUS and NGF was effectively reduced by URB597, but not by JZL184. Simultaneous inhibition of FAAH and MAGL did not improve the overall therapeutic response. Therefore, our findings indicate that enhancement of anandamide signaling with URB597 is a promising pharmacological approach for the alleviation of chronic widespread nociception in stress-exposed mice, and thus, it could represent a potential treatment strategy for chronic pain associated with neuropsychiatric disorders in humans.

show abstract

“…2-AG acts preferentially on CB 1 receptors in GABAergic neurons; in fact, the simulation of its synthesis was found to reduce GABAergic, but not glutamatergic neurotransmission [139,140]. Conversely, anandamide may inhibit the release of glutamate by activating CB 1 receptors in glutamatergic neurons [141].…”

Section: A Brief Outline On the Endocannabinoid Systemmentioning

confidence: 98%

Interactions of Cannabis and Amphetamine-Type Stimulants

Tambaro

Bortolato

2015

Cannabinoid Modulation of Emotion, Memory, and Motivation

View full text Add to dashboard Cite

Amphetamine-type stimulants (ATSs) are a large family of substances of abuse, characterized by well-known mood-and performance-enhancing properties. This class encompasses several high-potency stimulants and entactogens, such as the precursor compound d-amphetamine (AMPH), its synthetic N-methylated derivatives methamphetamine (METH) and 3, 4-methylenedioxy-N-methylamphetamine (MDMA, or "ecstasy"), as well as novel designer drugs, based on substituted forms of the natural alkaloid cathinone. ATSs (and in particular METH) are among the most commonly abused substances worldwide, second only to Cannabis sativa; indeed, the rate of concurrent consumption of METH and cannabis has been increasing over the last decade, particularly among adolescents. Anecdotal evidence suggests that marijuana may offset some unpleasant subjective effects of ATSs, such as anxiety and paranoia. Both drugs have been shown to increase schizophrenia vulnerability in young vulnerable individuals, raising the possibility that their concurrent intake may have synergistic effects with respect to the development of psychotic manifestations. In addition, the combination of these two substances may affect their subjective effects and exacerbate their abuse liability. Although current evidence on the neurobiological interactions of cannabis and ATSs remains mostly elusive, initial studies in animal models suggest that the cannabinoid system may play a relevant role in the motivational and addictive properties of ATSs; furthermore, cannabinoids may modify the behavioral effects and even attenuate some untoward long-term consequences of ATSs. In this chapter we review the available evidence on these potential interactions and outline some key mechanisms that may account for the mutual modulatory influence of these substances.

show abstract

Preservation of Striatal Cannabinoid CB1 Receptor Function Correlates with the Antianxiety Effects of Fatty Acid Amide Hydrolase Inhibition

Cited by 76 publications

References 56 publications

Neurobiological Interactions Between Stress and the Endocannabinoid System

Neurobiological Interactions Between Stress and the Endocannabinoid System

Therapeutic Potential of Inhibitors of Endocannabinoid Degradation for the Treatment of Stress-Related Hyperalgesia in an Animal Model of Chronic Pain

Interactions of Cannabis and Amphetamine-Type Stimulants

Contact Info

Product

Resources

About