Cabana-Domínguez, JuditMartín-García, ElenaGallego-Roman, AnaMaldonado, Rafael, 1961-Fernández-Castillo, NoèliaComand, Bru2022-03-182022-03-182021Cabana-Domínguez J, Martín-García E, Gallego-Roman A, Maldonado R, Fernández-Castillo N, Comand B.Reduced cue-induced reinstatement of cocaine-seeking behavior in Plcb1 +/- mice. Transl Psychiatry. 2021 Oct 11;11(1):521. DOI: 10.1038/s41398-021-01396-62158-3188http://hdl.handle.net/10230/52721Cocaine addiction causes serious health problems, and no effective treatment is available yet. We previously identified a genetic risk variant for cocaine addiction in the PLCB1 gene and found this gene upregulated in postmortem brains of cocaine abusers and in human dopaminergic neuron-like cells after an acute cocaine exposure. Here, we functionally tested the contribution of the PLCB1 gene to cocaine addictive properties using Plcb1+/- mice. First, we performed a general phenotypic characterization and found that Plcb1+/- mice showed normal behavior, although they had increased anxiety and impaired short-term memory. Subsequently, mice were trained for operant conditioning, self-administered cocaine for 10 days, and were tested for cocaine motivation. After extinction, we found a reduction in the cue-induced reinstatement of cocaine-seeking behavior in Plcb1+/- mice. After reinstatement, we identified transcriptomic alterations in the medial prefrontal cortex of Plcb1+/- mice, mostly related to pathways relevant to addiction like the dopaminergic synapse and long-term potentiation. To conclude, we found that heterozygous deletion of the Plcb1 gene decreases cue-induced reinstatement of cocaine-seeking, pointing at PLCB1 as a possible therapeutic target for preventing relapse and treating cocaine addiction.application/pdfeng© Juidit Cabana-Domínguez et al. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were madeCocaïnomaniaGenèticainfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/s41398-021-01396-6info:eu-repo/semantics/openAccess