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Publication : Reduced cue-induced reinstatement of cocaine-seeking behavior in Plcb1 +/- mice.

First Author  Cabana-Domínguez J Year  2021
Journal  Transl Psychiatry Volume  11
Issue  1 Pages  521
PubMed ID  34635637 Mgi Jnum  J:312769
Mgi Id  MGI:6788532 Doi  10.1038/s41398-021-01396-6
Citation  Cabana-Dominguez J, et al. (2021) Reduced cue-induced reinstatement of cocaine-seeking behavior in Plcb1 +/- mice. Transl Psychiatry 11(1):521
abstractText  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.
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