Cholecystokinin acts in the dorsomedial hypothalamus of young male rats to suppress appetite in a nitric oxide-dependent manner

• Published in: Neuroscience letters 2021-11, Vol.764, p.136295-136295, Article 136295
• Main Authors: Rust, Victoria A., Crosby, Karen M.
• Format: Article
• Language: English
• Subjects: Animals; Appetite Regulation - physiology; CCK2 receptors; Cholecystokinin; Cholecystokinin - administration & dosage; Cholecystokinin - metabolism; Dorsomedial Hypothalamic Nucleus - metabolism; Dorsomedial hypothalamus; Food intake; High fat diet; Humans; Male; Microinjections; Models, Animal; Nitric oxide; Nitric Oxide - metabolism; Pediatric Obesity - physiopathology; Pediatric Obesity - prevention & control; Rats; Rats, Sprague-Dawley; Receptor, Cholecystokinin B - metabolism
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2021.136295

•CCK decreases consumption of regular chow in young, male rats.•CCK acts through CCK2 receptors in the DMH to suppress appetite.•Nitric oxide mediates the effects of CCK on food intake in young, male rats.•CCK does not decrease the intake of high fat food in young, male rats. Cholecystokinin (CCK) is an appetite-suppressing hormone that acts in the dorsomedial hypothalamus (DMH) in adult rats to suppress food intake. It remains unknown, however, whether CCK has the same affect in young animals, despite the rising prevalence of childhood obesity and drastic need for research in this area. At the synaptic level, CCK has been shown to inhibit putative orexigenic DMH neurons in young male rats by increasing GABA release onto these neurons via a CCK2 receptor and nitric oxide-dependent pathway. Whether this pathway leads to appetite suppression in young rats is not known. We therefore investigated whether intra-DMH administration of CCK, with or without inhibitors of the CCK2 receptor and nitric oxide signaling pathways, affects food intake in young, male, fasted Sprague-Dawley rats. We implanted bilateral guide cannulas into the DMH and allowed animals to recover from the surgery. Animals were then fasted for 24 h, following which they received intra-DMH microinjections of vehicle, CCK-8S, or CCK-8S combined with either LY-225910 (CCK2 receptor antagonist), L-NAME (a nitric oxide synthase inhibitor), or ODQ (a soluble guanylate cyclase inhibitor) and were given access to regular chow. Following a two hour refeeding period during which food intake, latency to feed, and body weight were measured, brains were subsequently removed to confirm cannula placement in the DMH. The effect of CCK on these parameters in rats given a high fat diet were also measured. Here we show that intra-DMH administration of CCK suppresses food intake and body weight in young rats. This effect requires activation of CCK2 receptors and nitric oxide signaling. Finally, CCK has no effect on consumption of a high fat diet when administered into the DMH. Overall, these findings demonstrate a potential pathway through which CCK might suppress appetite in young rats.