A group of rats was divided into 6 subgroups. Two subgroups were treated with four successive injections (i.p.) of either saline (SAL) (1 mL/kg) or METH-HCl (10 mg/kg). The remaining subgroups were also treated with a low dose of epothilone (EpoD) (EpoDL; 0.5 mg/kg), high dose of EpoD (EpoDH; 5 mg/kg) or DMSO before, during, and after binge METH or saline. All animals were sacrificed 3 days later and the striatal lysates were analyzed for (A-F) DAergic markers, glial fibrillary acidic protein (GFAP, 50 kDa) and (I) caspase-3 (35 and 17 kDa). β-Actin was used as a loading control. EpoDL and EpoDH alone increased DAT immunoreactivity (2.3 fold and 1.6 fold, respectively); they have the opposite effects on DA (+44% and −48%, respectively). EpoDH/METH treatment potentiated METH-induced deficits in striatal (A) DA (−63% vs. 92%), (B) 3,4-dihydroxyphenylacetic acid (DOPAC) (−48% vs. −77%), and (F) dopamine transporter (DAT, 60–80 kDA) (−50% vs. −99%) as well as (D) METH-induced increase in DOPAC/DA ratio (+32% vs. +60%). Compared to DMSO/SAL, DA and DAT content in EpoDL/METH group was decreased by 63% and 50%, respectively, while compared to EpoDL/SAL these markers were decreased by 59% and 55%, respectively. (F) Tyrosine hydroxylase (TH, 60 kDa) content in EpoDH/METH group significantly decreased in relation to EpoDH/SAL group (−36%). (G) DMSO/METH and EpoDH/METH treatment increased GFAP immunoreactivity (+57% and +69%, respectively). (I) Neither treatment activated caspase-3. (I) Representative western blot images. Band density values were normalized to DMSO/SAL values. All data are expressed as mean ± SEM. *p<0.05, **p<0.01, ***p<0.001, treatment vs. DMSO/SAL, #p<0.05, ##p<0.01, ###p<0.001, EpoD/SAL vs. EpoD/METH, ∏ (bracket) p<0.05 differences within SAL and METH subgroups, one-way ANOVA followed by Tukey’s post hoc test, n=4–13. Analysis of DA, DAT and DOPAC/DA data by two-way ANOVA with Tukey post hoc test revealed co-treatment (DMSO, EpoD) × treatment (SAL, METH) interaction for DAT and DOPAC/DA ratio (F(2.43) = 7.17, p<0.01 and F(2,44) = 5.79, p<0.01, respectively).