Fig. 4: Epidermal stem cell-derived hBChE and GLP1 protect mice from reward and toxicity induced by co-administration of alcohol and cocaine.
a GhBChE/GLP1 and GWT mice were fed with doxycycline and underwent pre-test, alcohol (1 g/kg) and cocaine (10 mg/kg) conditioning and expression test. Data were plotted as means ± S.E.M. (n = 8 mice per group; treatment × days interaction by repeated-measures ANOVA: F1,14 = 13.46, P = 0.0025). Significance was tested by Fisher’s LSD test. ***P = 0.0003 on Day 6. b Cocaethylene concentration in the blood was determined by LC–MS/MS after cocaine and alcohol administration in GhBChE/GLP1 and GWT mice (n = 5 for each group; treatment × time interaction: F3,24 = 4.6, P = 0.0111, repeated-measures two-way ANOVA). Significance was tested with Fisher’s LSD test. *P = 0.0414, **P = 0.0035, and *P = 0.0165 at 15, 30, and 60 min, respectively. c Lethality rates after injection of multiple doses of cocaine-alcohol in GhBChE/GLP1 and GWT mice. Bars show means ± S.E.M. (Three independent experiments were performed and 6–8 mice were used for each experiment). Individual data points show the result from each experiment. Significance was tested by Student’s t test. t = 5.018, **P = 0.0074 at 60 mg/kg cocaine plus 2 g/kg ethanol injections; t = 7.895, **P = 0.0014 at 60 mg/kg cocaine plus 3 g/kg ethanol injections; t = 8, **P = 0.0013 at 60 mg/kg cocaine plus 5 g/kg ethanol injections.
