Figure 1.

(a) Milnacipran dose dependently reduces ethanol self-administration (number of ethanol deliveries) more efficiently in dependent rats compared with non-dependent rats. Ethanol dependence was induced by intermittent exposure to ethanol vapors for at least 10 weeks, and animals were then tested for ethanol self-administration after 6 h of acute withdrawal. Dependent rats (n=12) showed a significant increase in the number of ethanol deliveries compared with non-dependent rats (n=10). Milnacipran (i.p., 20 min before self-administration) significantly reduced ethanol self-administration in dependent animals, in a dose-dependent manner. In non-dependent rats, a significant effect was observed only at the highest dose. Values represent mean±SEM. ^#P<0.001 compared with the same milnacipran dose in non-dependent animals. ^***P<0.001, ^**P<0.01, and ^*P<0.05 compared with saline treatment in dependent animals. ^@P<0.05 one-way ANOVA with repeated measures compared with 0. (b) The day after milnacipran treatment (40 mg/kg), dependent and non-dependent rats showed the same level of response as compared with baseline. ^##P<0.01 compared with non-dependent rats, ^***P<0.001 compared with 0 within dependent rats, and ^@@P<0.01 compared with milnacipran 40 mg/kg within dependent animals.