Neurotrophin-4 knockout (NT4KO) mice have impaired short-term satiety associated with a loss of intestinal vagal intraganglionic laminar endings (IGLEs; Fox, J Neurosci, 21:8602, 2001). In contrast, mice overexpressing NT4 (NT4 knock-in mice, NT4KI; Fan, Nat Neurosci, 3:350, 2000) have an enhancement of some components of short-term satiety and preliminary results suggest they have increased IGLEs restricted to the intestine (Fox, 2003, SFN mtg). These different changes in satiety in NT4KO and NT4KI mice imply that altered vagal afferent signaling, rather than general disruption of intestinal function may have caused these perturbations of satiety. To further investigate this relationship, the effect of exogenous CCK-8 on short-term food intake, which is largely mediated by vagal gastrointestinal afferents, was examined in NT4KI mice (n=12) and wild types (n=9). Mice maintained on pelleted chow and water ad libitum were adapted to precision pellets (BioServ, 20mg). On test days sulfated CCK-8 (0.5, 1, 2, o...