Figure 3.

Both guanfacine (0.6 mg/kg) and naltrexone (2 mg/kg) significantly decreased alcohol intake compared with vehicle at the 4 h time point (a, left panel) in rats that had voluntarily consumed high amounts of alcohol for ∼6 months before the treatment (n=11). At the 24 h time point (a, right panel) only guanfacine significantly decreased the alcohol intake compared with vehicle. At both time points, guanfacine significantly decreased the alcohol intake compared with naltrexone. All values are expressed as mean±SEM; **P<0.01, ***P<0.001 compared with vehicle or as indicated (one-way repeated-measures ANOVA followed by planned comparisons). To evaluate the effect of guanfacine and naltrexone on the alcohol deprivation effect (ADE), two groups of rats voluntarily consuming (b) moderate (2.6±0.2 g/kg per 24 h) or (c) high (4.7±0.2 g/kg per 24 h) amounts of alcohol for at least 8 weeks were subjected to a period of 17 days with forced alcohol abstinence before alcohol was reintroduced. The rats were pretreated with guanfacine (0.6 mg/kg), naltrexone (2 mg/kg), or vehicle before renewed alcohol access (n=6–9 per treatment group). An ADE was present in vehicle-treated rats consuming moderate (b) but not high (c) amounts of alcohol. Both guanfacine- and naltrexone-treated rats significantly decreased their alcohol intake in both high (c) and moderate (b) drinkers compared with corresponding baseline before the abstinence period, with the effects of guanfacine being more pronounced and long lasting than naltrexone. All values are expressed as mean±SEM; *P<0.05, **P<0.01, ***P<0.001 compared with corresponding values before the abstinence period (paired Student's t-test within each treatment).