Cannabidiol decreases motivation for cocaine in a behavioral economics paradigm but does not prevent incubation of craving in mice

Alegre-Zurano, Laia; Berbegal-Sáez, Paula; Luján, Miguel Ángel; Cantacorps, Lídia; Martín‐Sánchez, Ana; García-Baos, Alba; Valverde, Olga

doi:10.1016/j.biopha.2022.112708

Cited by 10 publications

(7 citation statements)

References 68 publications

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“…Several proteins, including protein kinase C (PKC), casein kinase II (CK2), and endoplasmic reticulum kinase (ERK) can also phosphorylate Nrf2, leading to its dissociation from Keap1 and nuclear accumulation. Of these, only ERK has been shown to be positively regulated by CBD ( Alegre-Zurano et al, 2022 ).…”

Section: Cbd Promotes the Scavenging Of Ros/rns: Relevance For Ichmentioning

confidence: 99%

Anti-oxidant effects of cannabidiol relevant to intracerebral hemorrhage

Yan,

Zhang,

et al. 2023

Front. Pharmacol.

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Intracerebral hemorrhage (ICH) is a subtype of stroke with a high mortality rate. Oxidative stress cascades play an important role in brain injury after ICH. Cannabidiol, a major non-psychotropic phytocannabinoids, has drawn increasing interest in recent years as a potential therapeutic intervention for various neuropsychiatric disorders. Here we provide a comprehensive review of the potential therapeutic effects of cannabidiol in countering oxidative stress resulting from ICH. The review elaborates on the various sources of oxidative stress post-ICH, including mitochondrial dysfunction, excitotoxicity, iron toxicity, inflammation, and also highlights cannabidiol’s ability to inhibit ROS/RNS generation from these sources. The article also delves into cannabidiol’s role in promoting ROS/RNS scavenging through the Nrf2/ARE pathway, detailing both extranuclear and intranuclear regulatory mechanisms. Overall, the review underscores cannabidiol’s promising antioxidant effects in the context of ICH and suggests its potential as a therapeutic option.

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Section: Cbd Promotes the Scavenging Of Ros/rns: Relevance For Ichmentioning

confidence: 99%

Anti-oxidant effects of cannabidiol relevant to intracerebral hemorrhage

Yan,

Zhang,

et al. 2023

Front. Pharmacol.

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“…In rodent models of SUDs, cocaine SA is a learning process that primes the brain for motivation for drug in response to environmental or internal cues that invoke memory of the cocaine experience. This primed state intensi es over the course of abstinence, as demonstrated in both rats [19][20][21] and mice [22][23][24] , and is translationally relevant to humans 25 . We selected 2 publicly available RNA-seq datasets from mice that included treatment groups relevant to cocaine motivation and abstinence 17,18 .…”

Section: Methodsmentioning

confidence: 92%

An approach for prioritizing candidate genes from RNA-seq using preclinical cocaine self-administration datasets as a test case

Vannan

Dell’Orco²,

Perrone‐Bizzozero³

et al. 2023

Preprint

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RNA-sequencing (RNA-seq) technology has led to a surge of neuroscience research using animal models to probe the complex molecular mechanisms underlying brain function and behavior, including substance use disorders (SUDs). However, findings from rodent studies often fail to be translated into clinical treatments. Here, we developed a novel pipeline for narrowing candidate genes from preclinical studies by translational potential and demonstrated utility of this model in three RNA-seq studies of rodent self-administration. This pipeline uses evolutionary conservation and preferential expression of genes across brain tissues to prioritize candidate genes, increasing the translational utility of RNA-seq in model organisms. We found only 1 differentially-expressed gene (DEG) in any dataset after correcting for multiple testing (FDR < 0.05 or < 0.1), raising concerns about false positives and low statistical power that may impact these and other RNA-seq datasets. Thus, we demonstrate the utility of our prioritization pipeline using an uncorrected p-value. Curiously, even with an uncorrected p-value of 0.05 we saw low overlap of DEGs across the 3 selected datasets. Thus, we also advocate for improved RNA-seq data collection, statistical testing, and metadata reporting that will bolster the field’s ability to identify reliable candidate genes and compare results across studies.

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“…The breakpoint was defined as the number of nosepokes required to obtain the last pellet in the PR schedule. Finally, mice completed a demand task test modified from previous studies (Alegre-Zurano et al, 2022) where the criteria for earning a pellet followed an ascending trend every 10 minutes: 1, 2, 4, 6, 8, 11, 14, 18, 21, 28, 35, 42.…”

Section: Methodsmentioning

confidence: 99%

Lack of rhythmicity in Bmal1 deficient mice impairs motivation towards natural stimuli

Berbegal-Sáez,

Gallego-Landin,

Macía

et al. 2024

Preprint

Self Cite

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Maintaining appropriate circadian rhythmicity is essential for coordinating the activity of biological functions in mammalian organisms. A variety of physiological and behavioral changes have been associated with disturbances of this complex clock mechanism.In the present study, we delve into the consequences of circadian arrhythmia using the Bmal1-knockout (KO) mouse line aiming to explore potential behavioral and motivational implications. We were able to identify the intricate activity patterns that define circadian disturbance in Bmal1-KO mice by utilizing a new analysis model based on entropy divergence.Alterations in locomotor activity were accompanied by disruptions of circadian expression patterns in various clock genes as revealed by gene expression analysis. Additionally, we found a dysregulated gene expression profile in Bmal1-KO mice regarding genes related to circadian control in various brain nuclei. Specifically, the ventral striatum exhibited a dysregulation in the expression levels of genes modulating reward and motivation.Further investigation revealed that BMAL1 deficient mice showed a sustained rise in motivation and seeking behavior for food and water reinforcers in the self-administration paradigm, independently of the caloric content of the reward. Together, our data reveal that disruptions in circadian rhythmicity, induced by alterations in the molecular clock, also impact the gene expression regulating the reward system. This, in turn, can lead to altered seeking behavior and motivation for natural rewards. In summary, the present study contributes to our understanding of how reward processing is under the regulation of circadian clock machinery.

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Cannabidiol decreases motivation for cocaine in a behavioral economics paradigm but does not prevent incubation of craving in mice

Cited by 10 publications

References 68 publications

Anti-oxidant effects of cannabidiol relevant to intracerebral hemorrhage

Anti-oxidant effects of cannabidiol relevant to intracerebral hemorrhage

An approach for prioritizing candidate genes from RNA-seq using preclinical cocaine self-administration datasets as a test case

Lack of rhythmicity in Bmal1 deficient mice impairs motivation towards natural stimuli

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