Figure 5.

Knockdown of p75NTR in the DLS reduces binge drinking of alcohol. A, B, Ltv-shp75NTR or Ltv-shSCR was bilaterally infused at a titer of 2 × 10⁷ pg/ml into the DLS. A, Ltv-shp75NTR infects DLS neurons. Four weeks after virus infusion, slices containing the DLS were costained with anti-GFP (green) and anti-NeuN (red) or costained with anti-GFP and anti-GFAP antibodies. The left image depicts the specificity of the site of infection. The right images depict Ltv-shp75NTR infection of neurons (costaining of GFP with NeuN; top) but not glia (costaining GFP with GFAP; bottom). B, Ltv-shp75NTR-mediated knockdown of p75NTR. The DLS was dissected 4 weeks after virus infusion, and p75NTR and GAPDH protein levels were measured by Western blot analysis. Data are expressed as mean ratio of p75NTR to GAPDH ± SEM and presented as percentages of Ltv-shSCR control. C, Schematic representation of the behavioral experiment. Rats underwent IA20%-2BC alcohol for 7 weeks. High-drinking rats (baseline level of alcohol intake equal or higher than 3.5 g/kg/24 h) received a bilateral infusion of Ltv-shSCR or Ltv-shp75NTR into the DLS, and after 1 week of recovery, the alcohol-drinking procedure resumed. D, E, Alcohol intake (grams per kilogram per 30 min; D) and water intake (milliliters per kilogram per 30 min; E) were recorded 4 weeks after viral infection. Results are expressed as mean ± SEM. *p < 0.01; **p < 0.001 versus Ltv-shSCR (unpaired t test). n = 4 (B) or 7 per treatment (D, E).