The effect of cholecystokinin administration in the dorsomedial nucleus of the hypothalamus on food intake in young rats

Abstract

Cholecystokinin (CCK) is an appetite-suppressing hormone and neuropeptide that has recently been found to act in the dorsomedial nucleus (DMH), a key appetite-regulatory area of the hypothalamus. In a recent electrophysiology study using brain slice recordings from young rats, CCK was found to activate CCK2 receptors (CCK2R) and interact with nitric oxide (NO) to increase the release of the inhibitory neurotransmitter GABA onto appetite regulatory neurons in the DMH. However, it is unclear whether this is the pathway through which CCK supresses appetite, thus necessitating the use of in vivo studies in young rats to elucidate the function of this pathway in relation to CCK. In the current study, we implanted bilateral guide cannulas into the DMH of young, male rats and administered injections of either 1) vehicle (aCSF), 2) CCK, 3) CCK + a NO synthase inhibitor, 4) CCK + a CCK2 receptor antagonist or 5) a NO synthase inhibitor, into food deprived animals. Following injections food intake, change in body weight and latency to feed were measured over a two-hour period. We also looked at the effect of CCK in young rats given a high fat diet (HFD) using two treatments 1) vehicle (aCSF) + HFD and 2) CCK + HFD. We found that CCK suppresses food intake in young rats and does so through interactions with NO but not CCK2 receptors in the DMH. We also found that the appetite suppressing effects of CCK had no impact on latency to feed. Finally, CCK was unable to suppress appetite in rats given high fat food. By confirming that CCK supresses appetite through NO signaling in the DMH this project provides a potential therapeutic target for future drugs to combat obesity.