Cannabinoid Receptor Type 2 Agonist Reduces Morphine Tolerance via Mitogen Activated Protein Kinase Phosphatase Induction and Mitogen Activated Protein Kinase Dephosphorylation

•Repeated morphine treatment reduced MKP-1/3 expression in the spinal cord.•AM1241 increased the expression of spinal MKP-1/3 in morphine tolerant mice.•AM1241 reduced MAPK phosphorylation by increasing MKP-1/3 expression.•The effect of AM1241 on morphine tolerance was blocked by MKP-1/3 antagonist.