Figure 4
Downregulation of glial cell line-derived neurotrophic factor (GDNF) expression in the ventral tegmental area (VTA) prevents the sustained, but not the rapid, effects of recombinant GDNF (rGDNF) on alcohol consumption. Rats consumed a solution of 20% alcohol for 7 weeks. After the establishment of a baseline level of alcohol intake, VTA were infected with adenovirus (AdV)-shGDNF or control AdV-shSCR (SCR), after which the basal levels of alcohol intake were reestablished. Ten to 15 days after the infection, rGDNF (10 μg per side) or vehicle was infused into the VTA 10 min before the drinking session onset. Data are expressed as mean±s.e.m. of alcohol intake in g kg−1 (*P<0.01 vs vehicle; n=7). (a) Alcohol intake during the first 30 min of the drinking session (main effects of rGDNF infusion (F (1,12)=40.55, P<0.0001) and of viral infection (F (1,12)=4.89, P<0.05), but no interaction (F (1,12)=0.10, P=0.75)). (b) Alcohol intake during the 4–24 h time period after the beginning of the drinking session (mixed-model analysis of variance (ANOVA): a main effect of rGDNF infusion (F (1,12)=6.67, P<0.025), no effect of viral infection (F (1,12)=2.53, P=0.13), and a marginally significant interaction (F (1,12)=3.88, P=0.072). Post-hoc comparisons: a difference between rGDNF- and vehicle-infused rats in the adenovirus (AdV)-shSCR infected control rats (P<0.01), but not in rats that were infected with AdV-shGDNF (P=0.67)).
