Reduced cue-induced reinstatement of cocaine-seeking behavior in Plcb1 +/- mice
Por:
Cabana-Domínguez J, Martin-Garcia, E, Gallego-Roman, A, Maldonado, R, Fernandez-Castillo N and Cormand B
Publicada:
11 oct 2021
Ahead of Print:
11 oct 2021
Resumen:
Cocaine 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.
Filiaciones:
Cabana-Domínguez J:
Department de Genètica, Microbiologia i Estadística, Facultat de Biologia, Universitat de Barcelona, Barcelona, Catalonia, Spain
Institut de Biomedicina de la Universitat de Barcelona (IBUB), Barcelona, Catalonia, Spain
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain
Institut de Recerca Sant Joan de Déu (IR-SJD), Barcelona, Catalonia, Spain
Martin-Garcia, E:
Laboratory of Neuropharmacology-Neurophar, Department of Experimental and Health Sciences, Universitat Pompeu Fabra (UPF), Barcelona, Catalonia, Spain
Hospital del Mar Medical Research Institute (IMIM), Barcelona, Catalonia, Spain
Gallego-Roman, A:
Laboratory of Neuropharmacology-Neurophar, Department of Experimental and Health Sciences, Universitat Pompeu Fabra (UPF), Barcelona, Catalonia, Spain
Maldonado, R:
Laboratory of Neuropharmacology-Neurophar, Department of Experimental and Health Sciences, Universitat Pompeu Fabra (UPF), Barcelona, Catalonia, Spain
Hospital del Mar Medical Research Institute (IMIM), Barcelona, Catalonia, Spain
Fernandez-Castillo N:
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain.
Institut de Recerca Sant Joan de Déu (IR-SJD), Barcelona, Catalonia, Spain.
Institut de Biomedicina de la Universitat de Barcelona (IBUB), Barcelona, Catalonia, Spain.
Department de Genètica, Microbiologia i Estadística, Facultat de Biologia, Universitat de Barcelona, Barcelona, Catalonia, Spain.
gold, Green Submitted, Green Published
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