Endocannabinoids regulate cocaine-associated memory through brain AEA–CB1R signalling activation

Li, Hongchun; Chen, Rong; Zhou, Yuanyi; Wang, Haichuan; Sun, Luqiang; Lin, Bingcheng; Zhang, Jie

doi:10.1016/j.molmet.2022.101597

Cited by 5 publications

(2 citation statements)

References 55 publications

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“…Furthermore, genetic studies have suggested that dysfunction of the enzymatic machinery could modulate eCBs concentrations. For example, the inhibition of the fatty acid amide hydrolase (FAAH), an enzyme involved in the degradation of AEA, has been related to increased AEA concentrations, but to an absence of significant changes in 2-AG or even, to decreased concentrations [27,71,[76][77][78]. Altogether, these possibilities represent some of many factors that could underlie a dysfunctional eCB system and serve as a basis for future studies.…”

Section: Discussionmentioning

confidence: 99%

Anandamide and 2-arachidonoylglycerol baseline plasma concentrations and their clinical correlate in gambling disorder

Baenas,

Solé-Morata,

Granero

et al. 2023

Eur. Psychiatr.

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Introduction Different components of the endocannabinoid (eCB) system such as their most well-known endogenous ligands, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), have been implicated in brain reward pathways. While shared neurobiological substrates have been described among addiction-related disorders, information regarding the role of this system in behavioral addictions such as gambling disorder (GD) is scarce. Aims Fasting plasma concentrations of AEA and 2-AG were analyzed in individuals with GD at baseline, compared with healthy control subjects (HC). Through structural equation modeling, we evaluated associations between endocannabinoids and GD severity, exploring the potentially mediating role of clinical and neuropsychological variables. Methods The sample included 166 adult outpatients with GD (95.8% male, mean age 39 years old) and 41 HC. Peripheral blood samples were collected after overnight fasting to assess AEA and 2-AG concentrations (ng/ml). Clinical (i.e., general psychopathology, emotion regulation, impulsivity, personality) and neuropsychological variables were evaluated through a semi-structured clinical interview and psychometric assessments. Results Plasma AEA concentrations were higher in patients with GD compared with HC (p = .002), without differences in 2-AG. AEA and 2-AG concentrations were related to GD severity, with novelty-seeking mediating relationships. Conclusions This study points to differences in fasting plasma concentrations of endocannabinoids between individuals with GD and HC. In the clinical group, the pathway defined by the association between the concentrations of endocannabinoids and novelty-seeking predicted GD severity. Although exploratory, these results could contribute to the identification of potential endophenotypic features that help optimize personalized approaches to prevent and treat GD.

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Section: Discussionmentioning

confidence: 99%

Anandamide and 2-arachidonoylglycerol baseline plasma concentrations and their clinical correlate in gambling disorder

Baenas,

Solé-Morata,

Granero

et al. 2023

Eur. Psychiatr.

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“…URB597 does not alter cocaine-induced hyperlocomotion [50], but it does protect against cocaine-induced neurotoxicity [51]. Moreover, URB597 increases the preference for the cocaine-paired compartment in the conditioned place preference (CPP) paradigm [52], whereas in the intravenous self-administration model, it elicits different effects depending on the administration protocol. Therefore, acute URB597 treatment does not affect cocaine self-administration in rats [53] or squirrel monkeys [54], but it decreases both cue- and cocaine-induced reinstatement in rats [53].…”

Section: Introductionmentioning

confidence: 99%

The FAAH inhibitor URB597 reduces cocaine seeking during conditioned punishment and withdrawal

Alegre-Zurano

García-Baos

Castro‐Zavala

et al. 2023

Preprint

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The endocannabinoid system is prominently implicated in the control of cocaine reinforcement due to its relevant role in synaptic plasticity and neurotransmitter modulation in the mesocorticolimbic system. The inhibition of fatty acid amide hydrolase (FAAH), and the resulting increase in anandamide and other N-acylethanolamines, represents a promising strategy for reducing drug seeking. In the present study, we aimed to assess the effects of the FAAH inhibitor URB597 (1 mg/kg) on crucial features of cocaine addictive-like behaviour in mice. Therefore, we tested the effects of URB597 on acquisition of cocaine (0.6 mg/kg/inf) self-administration, compulsive-like cocaine intake and cue-induced drug-seeking behaviour during withdrawal. URB597 reduced cocaine intake under conditioned punishment while having no impact on acquisition. This result was associated to increased cannabinoid receptor 1 gene expression in the ventral striatum and medium spiny neurons activation in the nucleus accumbens shell. Moreover, URB597 reduced cue-induced drug-seeking behaviour during prolonged abstinence and prevented the withdrawal-induced increase in FAAH gene expression in the ventral striatum. In this case, URB597 decreased activation of medium spiny neurons in the nucleus accumbens core. Our findings evidence the prominent role of endocannabinoids in the development of cocaine addictive-like behaviours and support the potential of FAAH inhibition as a therapeutical target for the treatment of cocaine addiction.

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The FAAH inhibitor URB597 reduces cocaine intake during conditioned punishment and mitigates cocaine seeking during withdrawal

Zurano¹,

García-Baos²,

Castro‐Zavala³

et al. 2023

Biomedicine & Pharmacotherapy

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Endocannabinoids regulate cocaine-associated memory through brain AEA–CB1R signalling activation

Cited by 5 publications

References 55 publications

Anandamide and 2-arachidonoylglycerol baseline plasma concentrations and their clinical correlate in gambling disorder

Anandamide and 2-arachidonoylglycerol baseline plasma concentrations and their clinical correlate in gambling disorder

The FAAH inhibitor URB597 reduces cocaine seeking during conditioned punishment and withdrawal

The FAAH inhibitor URB597 reduces cocaine intake during conditioned punishment and mitigates cocaine seeking during withdrawal

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