Inhibition of c-Src attenuates morphine tolerance. (A) Dasatinib (n = 8) reduced tolerance in μ+/- mice compared to vehicle injections (n = 8). Data identified with asterisks were significantly different from equivalent vehicle data (*p < 0.05, Kruskall-Wallis test, post hoc Dunn’s correction). (B) Western blot showing total c-Src (left panel) and phosphorylated c-Src (right panel) extracted from SW620 colon cancer cells treated with either DMSO (vehicle), PP2 (10 μM), dasatinib (10 μM) or PP3 (10 μM). β-Actin was used as a loading control. PP2 and dasatinib reduced phosphorylated c-Src levels, while PP3 had no effect relative to vehicle. (C) The relatively selective c-Src inhibitor, PP2 (5 mg/Kg i.p.), also attenuated the development of morphine tolerance, while the inactive analogue, PP3 (5 mg/Kg i.p.) did not. Data identified with asterisks were significantly different from equivalent PP3 data (*p < 0.01, Kruskall-Wallis test, post hoc Dunn’s correction). Data are presented as median ± IQR.