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Elucidating cannabinoid biology in zebrafish (Danio rerio).

Randall G Krug, Karl J Clark

Gene July 17, 2015 DOI: 10.1016/j.gene.2015.07.036 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Review Peer reviewed
Population Zebrafish (Danio rerio) and rodent models, as covered in the reviewed literature
Topics Cannabis
Keywords Animals Zebrafish Cannabinoids Endocannabinoid Synthetic cannabinoid Phytocannabinoid
Key findings Argues that the zebrafish model, with its cannabinoid receptor genes cnr1 and cnr2 and associated synthesis and degradation enzymes, offers a genetically tractable system for investigating both the toxicological consequences and therapeutic potential of altered endocannabinoid signaling. The authors propose that integrating zebrafish findings with rodent studies can guide future cannabinoid research, which they describe as increasingly significant given recent trends in cannabis legislation.

Abstract

The number of annual cannabinoid users exceeds 100,000,000 globally and an estimated 9% of these individuals will suffer from dependency. Although exogenous cannabinoids, like those contained in marijuana, are known to exert their effects by disrupting the endocannabinoid system, a dearth of knowledge exists about the potential toxicological consequences on public health. Conversely, the endocannabinoid system represents a promising therapeutic target for a plethora of disorders because it functions to endogenously regulate a vast repertoire of physiological functions. Accordingly, the rapidly expanding field of cannabinoid biology has sought to leverage model organisms in order to provide both toxicological and therapeutic insights about altered endocannabinoid signaling. The primary goal of this manuscript is to review the existing field of cannabinoid research in the genetically tractable zebrafish model-focusing on the cannabinoid receptor genes, cnr1 and cnr2, and the genes that produce enzymes for synthesis and degradation of the cognate ligands anandamide and 2-arachidonylglycerol. Consideration is also given to research that has studied the effects of exposure to exogenous phytocannabinoids and synthetic cannabinoids that are known to interact with cannabinoid receptors. These results are considered in the context of either endocannabinoid gene expression or endocannabinoid gene function, and are integrated with findings from rodent studies. This provides the framework for a discussion of how zebrafish may be leveraged in the future to provide novel toxicological and therapeutic insights in the field of cannabinoid biology, which has become increasingly significant given recent trends in cannabis legislation.

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Cognitive Impairment Induced by Delta9-tetrahydrocannabinol Occurs through Heteromers between Cannabinoid CB1 and Serotonin 5-HT2A Receptors Mice 2015 Preclinical study
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Long-term hippocampal interneuronopathy drives sex-dimorphic spatial memory impairment induced by prenatal THC exposure Mice prenatally exposed to THC, including conditional CB1R knockout mice 2020 Animal experimental study
Chronic cannabis promotes pro-hallucinogenic signaling of 5-HT2A receptors through Akt/mTOR pathway Mice exposed to chronic THC early in life 2018 Animal experimental study
Effects of cannabinoid drugs on the deficit of prepulse inhibition of startle in an animal model of schizophrenia: the SHR strain Spontaneously hypertensive rats (SHRs) and Wistar rats 2014 Animal experimental study

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