Cabana Domínguez, JuditMartín-García, ElenaGallego-Roman, AnaMaldonado, Rafael, 1961-Fernàndez Castillo, NoèliaCormand Rifà, Bru2022-01-142022-01-142021-10-112158-3188https://hdl.handle.net/2445/182331Cocaine 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.11 p.application/pdfengcc-by-nc-nd (c) Cabana Domínguez, Judit et al., 2021https://creativecommons.org/licenses/by-nc-nd/4.0/DrogoaddiccióGenèticaCocaïnaDrug addictionGeneticsCocaineinfo:eu-repo/semantics/article7155352022-01-14info:eu-repo/semantics/openAccess