loading page

Reduced cue-induced reinstatement of cocaine-seeking behavior in Plcb1+/- mice
  • +3
  • Judit Cabana-Dominguez,
  • Elena Martin-Garcia,
  • Ana Gallego-Roman,
  • Rafael Maldonado,
  • Noèlia Fernàndez-Castillo,
  • Bru Cormand
Judit Cabana-Dominguez
Universitat de Barcelona
Author Profile
Elena Martin-Garcia
Universitat Pompeu Fabra
Author Profile
Ana Gallego-Roman
Laboratori de Neurofarmacologia. Universitat Pompeu Fabra
Author Profile
Rafael Maldonado
Laboratori de Neurofarmacologia. Universitat Pompeu Fabra
Author Profile
Noèlia Fernàndez-Castillo
Universitat de Barcelona
Author Profile
Bru Cormand
Universitat de Barcelona
Author Profile

Abstract

Background and Purpose: 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 PLCB1 gene to cocaine addictive properties in mice. Experimental approach: We used heterozygous Plcb1 knockout mice (Plcb1+/-) and characterized their behavioral phenotype. Subsequently, mice were trained for operant conditioning and self-administered cocaine for 10 days. Plcb1+/- mice were assessed for cocaine motivation, followed by 26 days of extinction and finally evaluated for cue-induced reinstatement of cocaine seeking. Gene expression alterations after reinstatement were assessed in medial prefrontal cortex (mPFC) and hippocampus (HPC) by RNAseq. Key Results: Plcb1+/- mice showed normal behavior, although they had increased anxiety and impaired short-term memory. Importantly, after cocaine self-administration and 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. Conclusions and Implications: 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.