Figure 5.

Intra-VTA infusion of GDNF produces a downward shift in the dose–response curve for alcohol. A–E, An illustrative theoretical dose–response curve for drug self-administration and its modulation by pharmacological agents. A, B, Number of operant responses (A) and the resulting drug intake (B) as a function of the dose of the presented drug. C–E, Pharmacological agents (potential therapeutics) can reduce self-administration at a relevant reinforcing dose of the drug of abuse (represented by the open and solid circle for the vehicle and treatment condition, respectively) by shifting the dose–response curve to the right (“antagonist” effect) (C), or to the left (“agonist” effect, that substitutes for the rewarding effects of the drug) (D), or by inducing a downward shift (direct inhibition of the reinforcing effect of the drug) (E). F, G, GDNF (10 μg/μl/side) or vehicle was infused into the VTA 10 min before 30 min operant oral alcohol self-administration sessions of 2.5, 10, 20, and 40% alcohol. F, Mean ± SEM of the number of alcohol deliveries. G, Mean ± SEM of the alcohol intake (grams/kilogram). n = 9. **p < 0.01; ***p < 0.001.