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GPCR and Alcohol-Related Behaviors in Genetically Modified Mice

Abstract : G protein-coupled receptors (GPCRs) constitute the largest class of cell surface signaling receptors and regulate major neurobiological processes. Accordingly, GPCRs represent primary targets for the treatment of brain disorders. Several human genetic polymorphisms affecting GPCRs have been associated to different components of alcohol use disorder (AUD). Moreover, GPCRs have been reported to contribute to several features of alcohol-related behaviors in animal models. Besides traditional pharmacological tools, genetic-based approaches mostly aimed at deleting GPCR genes provided substantial information on how key GPCRs drive alcohol-related behaviors. In this review, we summarize the alcohol phenotypes that ensue from genetic manipulation, in particular gene deletion, of key GPCRs in rodents. We focused on GPCRs that belong to fundamental neuronal systems that have been shown as potential targets for the development of AUD treatment. Data are reviewed with particular emphasis on alcohol reward, seeking, and consumption which are behaviors that capture essential aspects of AUD. Literature survey indicates that in most cases, there is still a gap in defining the intracellular transducers and the functional crosstalk of GPCRs as well as the neuronal populations in which their signaling regulates alcohol actions. Further, the implication of only a few orphan GPCRs has been so far investigated in animal models. Combining advanced pharmacological technologies with more specific genetically modified animals and behavioral preclinical models is likely necessary to deepen our understanding in how GPCR signaling contributes to AUD and for drug discovery.
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https://hal-u-picardie.archives-ouvertes.fr/hal-03590705
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Soumis le : lundi 28 février 2022 - 10:07:33
Dernière modification le : mardi 8 mars 2022 - 03:29:13

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Jeremie Neasta, Emmanuel Darcq, Jerome Jeanblanc, Sebastien Carnicella, Sami Ben Hamida. GPCR and Alcohol-Related Behaviors in Genetically Modified Mice. Neurotherapeutics, Springer Verlag, 2020, 17 (1, SI), pp.17-42. ⟨10.1007/s13311-019-00828-y⟩. ⟨hal-03590705⟩

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