Figure 7. Food restriction enhances desensitization of D2 autoreceptors. Using a potassium-based pipette solution, we measured the GIRK channel D2 autoreceptor-mediated outward current that occurs in response to a maximal iontophoresis of DA (1 m). A, Iontophoresis was repeated every 6 min (black arrows) until a stable baseline was obtained, at which time the DAT inhibitor cocaine (10 μm) was applied by bath perfusion. Numbered events from A are enlarged in B to better show outward currents that were observed before and after the application of cocaine (B, top) or dopamine (B, bottom). B, C, During washout from a 12 min application of cocaine, we observed that the currents (B, example trace 1 vs example trace 2) recovered significantly more slowly in neurons from food-restricted mice (C). To determine whether this difference is due directly to the activation of D2 autoreceptors, we conducted a separate experiment where desensitization was induced by a long (50 s) iontophoretic pulse of dopamine (large gray arrow in A). We observed a diminished recovery from desensitization (B, example trace 3 vs example trace 4) in neurons from food-restricted mice (D). The data point in D immediately following the iontophoretic pulse indicates the remaining outward current at the end of that pulse. *p < 0.05, **p < 0.01, ***p < 0.001. Food Rest, Food restricted; Ad Lib, ad libitum.