Fig. 5: Systemic naltrexone pretreatment and intra-mPFC anti-β-endorphin antibody infusion block the molecular effects of ketamine.

A Schematic timeline of systemic naltrexone pretreatment, ketamine treatment, and tissue collection. Systemic naltrexone pretreatment blocks (B) the increase in phosphorylation of GluR1 (interaction: F(1, 18) = 6.515, p = 0.0200) and (C) the trend-level increase in phosphorylation of μ-ORs at Ser375 in the total homogenate induced by ketamine at 1 h. D Systemic naltrexone pretreatment blocks total GluR1 levels in the synaptosomes induced by ketamine at 24 h (ketamine main effect: F(1, 17) = 5.492, p = 0.0315; naltrexone main effect: F(1, 17) = 6.673, p = 0.0193). E Schematic timeline of intra-mPFC anti-β-endorphin neutralizing antibody pretreatment, ketamine treatment, and tissue collection. Intra-mPFC anti-β-endorphin neutralizing antibody pretreatment blocks (F) the trend-level increase in GluR1 phosphorylation (interaction: F(1, 20) = 4.507, p = 0.0464) and (G) the increase in phosphorylation of μ-ORs at Ser375 (interaction: F(1, 20) = 8.095, p = 0.0100) in the total homogenate at 1 h. H Intra-mPFC anti-β-endorphin neutralizing antibody pretreatment blocks the increase in total GluR1 levels in the synaptosomes at 24 h (interaction: F(1, 16) = 3.514, p = 0.0792; ketamine main effect: F(1, 16) = 4.980, p = 0.0403; antibody main effect: F(1, 16) = 4.809, p = 0.0434). Two-way ANOVA followed by Sidak’s post hoc test. n = 5 for S/S and S/K, n = 6 for N/S and N/K in B and C; n = 5 for S/S, N/S, N/K and n = 6 for S/K in D; n = 6/group in F and G; n = 5/group in H. Post hoc significant effects indicated as: *p < 0.05. SAL/S saline, NTX/N naltrexone, K ketamine, IgG/I control IgG, Ab/E anti-β-endorphin neutralizing antibody.