Figure 5: Psilocybin pretreatment blunts heroin relapse and regulates gene expression of inflammatory cytokine and chemokines in the PFC during inhibition of heroin seeking.

(A) Overview of experiment. Animals underwent heroin SA for 10 days, 21D forced abstinence and then a 30-minute relapse test. Animals were pretreated with a single dose of 3.0 mg/kg psilocybin or saline vehicle either 4 or 24 hr prior to the test. Animals were euthanized within 1 hour of completion of the relapse test. (A-F) Shown are drug-paired active or inactive lever presses (B, E) and heroin infusions during SA (C, D, F) for each group, prior to any psilocybin treatment. Animals were balanced for lever responses and heroin infusions (D-F) on day 10 of SA. (G) Active and inactive lever presses during the relapse test for rats that received 3 mg/kg psilocybin 4 or 24 hr prior to testing. Asterisk above solid line denotes p<0.05 for Kruskal-Wallis test; * directly above histogram denotes p<0.05 vs vehicle for Post hoc test. Error bars indicate mean +/− S.E.M. n=8–15/group. (H-I) Volcano plot depicting inflammatory cytokine and chemokine genes, obtained by qPCR array, that were differentially expressed in the PFC of rats that were treated with 3.0 mg/kg psilocybin 4 hr (H) or 24 hr (I) prior to a relapse test, vs vehicle treated animals. Horizontal dotted line denotes p value of 0.05. Vertical dotted line denotes fold change of +/− 30%. Grey circles represent genes that were not significantly altered. Red dots represent genes that meet criteria for significance (J-K) Results of correlation analysis of relapse behavior of rats (from G) with inflammatory cytokine or chemokine gene expression data for the PFC that had psilocybin 4 hr (J) or 24 hr (K) prior to a relapse test. Italicized, bolded values were statistically significant.