Fig. 4

a, b Self-administration: ML375 significantly reduces operant self-administration of 10% ethanol (a; P = 0.0015; n = 14), but not sucrose (b; P = 0.96; n = 9) or water in iP rats. ML375 was dosed at 30 mg/kg (p.o.) at 27 h, 11 h and 3 h prior to testing. White bars represent ethanol (a) and sucrose (b) responses following vehicle treatment, respectively; dashed bars represent ethanol (a) or sucrose (b) responses following ML375 treatment; black bars represent water responses. Data were analysed by repeated measures two-way ANOVA with post hoc Tukey’s multiple comparisons test and expressed as mean ± S.E.M. **P < 0.01 denotes significant effect of ML375 treatment on active lever responding for ethanol compared to vehicle. There was no difference in responding for the water-paired lever after ML375 vs. vehicle treatment (P = 0.98). c, d Locomotor activity: There was no significant effect of ML375 (30 mg/kg, p.o.; c, dashed bar) compared to vehicle (white bar; n = 6) on locomotor activity in iP rats (P = 0.53). In contrast, a higher dose of ML375 (56.6 mg/kg, p.o. d, dashed bar) significantly reduced locomotor activity compared to vehicle (n = 9; P = 0.016). Data represent mean ± S.E.M. Data were analysed by repeated measures two-way ANOVA. e Cue-induced reinstatement: ML375 attenuates cue-induced reinstatement of ethanol seeking after systemic administration (3 × 30 mg/kg, p.o.; n = 11). Data were analysed by repeated measures two-way ANOVA with post hoc Tukey’s multiple comparison test and expressed as mean ± S.E.M. ****P < 0.0001 denotes significant difference of treatment on active lever responding during the reinstatement session as compared to extinction (P < 0.0001). ^#P < 0.05 denotes significant difference in active lever responding during reinstatement test between ML375 treated rats compared to vehicle (P = 0.015). There was no effect on inactive lever responding during cue-induced reinstatement test