Figure 3.

The anxiety-evoking cue affected mRNA expression of multiple CBD targets in the nucleus accumbens shell (NAcSh; A) and the NAcSh transcriptome (B-E). In the NAcSh, Cnr1, Faah, Gpr55, Htr1a, Gria1, and Fos were all significantly impacted by the cue (A). CBD significantly reversed the downregulation of Cnr1 and upregulation of Faah with similar effect, but not significant, for Gpr55 and Htr1a. RNAseq of the NAcSh revealed strong perturbation of the transcriptome in vehicle cue animals (B). Specific enrichment was observed for changes in synaptic plasticity related transcripts, epigenetic factors, and mitochondrial processes. In CBD animals, the effect of the salient cue was markedly diminished, with enrichment observed for LXR, prostaglandin biosynthesis, H3K27me3, and transcription factors (C). Examining the DEGs in the cue*drug interaction analysis, 1118 DEGs overlapped with significant effects of cue in the vehicle animals (D). These transcripts were almost entirely reversed in CBD animals (D, bottom panel, grey and orange genes are the same genes observed in vehicle cue animals). Ingenuity Pathway Analysis revealed the genes affected by the cue again related to plasticity, synaptic signaling, and mitochondrial dysfunction with predicted recruitment of levodopa, ACOX1, PPAR-α, RHO, and others (E). CBD reversed all of the effects observed in the vehicle cue animals. qPCR bar graphs represent means +/− the SEM.*p<0.05, **p<0.01.