(A) Raw traces recorded before (Control), during (Ghrelin), and after (Washout) application of ghrelin. (B) Time course of the ghrelin-induced increase in frequency of action potential (FAP). A–C represent time points when traces from A were recorded. (C and D) Mean frequency of action potentials recorded in mice (C) and rats (D) before, during, and after application of ghrelin. Hyperpolarization-induced action current recorded from DA neurons is shown (D, inset). (E and F) Ghrelin-mediated enhancement of action potential generation in VTA DA neurons required excitatory inputs. Shown are mean frequency of action potentials recorded before, during, and after application of ghrelin. (E) No effect of ghrelin was observed on frequency of action potentials in slices from GHSR-knockout mice (n = 5). (F) In the absence of excitatory input onto DA neurons, no effect of ghrelin was observed on frequency of action potentials in slices from wild-type mice (n = 6) in the presence of CNQX (10 μM) and AP5 (50 μM) in all solutions. Results were pooled from all recorded neurons. (G) Experiments were performed in slices from wild-type mice (n = 7) in the presence of bicuculline (30 μM) in all solutions. Results were pooled from all recorded neurons. In the absence of inhibitory inputs of DA neurons, ghrelin elevated the frequency of action potentials of VTA DA neurons, an effect that diminished after washout.