Fig 2: Gene expression changes in mPFC after cue-induced reinstatement of cocaine-seeking in Plcb1+/- vs wild-type (WT) mice.A Selection of over-represented KEGG pathways (Kyoto Encyclopedia of Genes and Genomes) and (B) GO (Gene Ontology) identified by DAVID software among the differentially expressed genes. The number of genes with altered expression included in each category is indicated on the right side of the bar. In red, relevant pathways for the addictive process. C Gene network involved in cellular development, cellular growth and proliferation, nervous system development and function (score = 62). The green nodes in the pathway indicate genes with downregulated expression in Plcb1+/- identified in RNAseq.

Fig 3: Behavioral tests for phenotype characterization.A Timeline of the experimental sequence. B, C Short-term memory measured in the V-maze for novel object recognition task, (B) discrimination index (t-test, **P < 0.01 vs WT) and (C) exploration. D Locomotor and (E) rearing activity measured in actimetry boxes (U-Mann–Whitney, **P < 0.01 vs WT). F Anxiety-like behavior measured by the time spent in the open arms (t-test, **P < 0.01 vs WT) and (G) the percentage of time in the open arms in the elevated plus maze (t-test, **P < 0.01 vs WT). Motor coordination measured in the rota rod test by the (H) number of r.p.m. that the mice performed in the average trials or the (I) mean time they remain in the apparatus. All data are expressed in median and interquartile range and individual data are shown (WT n = 25; Plcb1+/- n = 12).

Fig 4: Alterations in expression in the dopaminergic synapse in mPFC of Plcb1+/- mice after cue-induced reinstatement of cocaine-seeking.Adapted from KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways (mmu04728). Enriched pathway in differentially expressed genes in mPFC, 25 out of 131 genes in the pathway were differentially expressed (Praw = 2e-03; Pajd = 0.02). In red, upregulated genes and in green, downregulated genes in mPFC. *Protein complexes including upregulated and downregulated genes. Correspondence between genes and proteins can be found in Supplementary Table S6.