Figure 5. Ghrelin alters dopamine turnover and feeding via the VTA.
(A) Peripheral ghrelin treatment (1 mg/kg) was effective in increasing DA turnover in the nucleus accumbens of rats (n = 12). (B) Ghrelin treatment (30 or 100 μg) of ghrelin-deficient mice increased DA turnover in the ventral striatum in a dose-dependent manner compared with saline-treated mice. Conversely, ghrelin induced no alterations in DA turnover of the nucleus accumbens in Ghsr–/– mice (n = 5 per treatment). (C) VTA ghrelin infusions (0.5 μg in 0.5 μl saline) significantly increased food intake in rats compared with saline infusions or with infusions at sites adjacent to, but not in, the VTA (Sham). (D) Ghrelin (5 μg in 0.1 ml saline) injected i.p. increased food intake compared with saline-injected rats, an effect blocked by BIM28163 infusion (0.5 ng in 0.5 μl saline) directly into the VTA. (E and F) Rebound feeding 6 hours after fasting was significantly attenuated in mice treated with BIM12863 (1 nM/d) infused into the VTA at 0.25 μl/h (E). This effect was statistically significant only during the first hour after food was reintroduced (F). (G and H) Six-hour food intake in ghrelin- (G) and GHSR-deficient (H) mice under a restricted feeding schedule. Both ghrelin- and GHSR-deficient mice showed attenuated feeding responses after repeated overnight fasts. †P < 0.05 versus respective controls. #P < 0.05 versus saline/saline and BIM28163/saline treatment groups; ##P < 0.05 versus saline/ghrelin treatment group.