ABSTRACT
BACKGROUND: Several studies have reported that cholecystokinin (CCK), a short-term meal related satiety signal, and leptin, long-term signal for controlling feeding behaviour and body weight, act synergistically to inhibit food intake. However the mechanism and neuroanatomical basis for this response remain unclear. To clarify the neuronal mechanisms underlying the synergistic interaction between leptin and CCK, we examined the neuron activated by single or combined injection of leptin and CCK in fasted rats using immunohistochemistry for Fos. The expression of Fos can be used to trace neuronal activation pathways. METHODS: The rats were divided into 4 groups; Tris solution-saline, Tris solution-CCK, leptin-saline, leptin-CCK. Rats were received a single intracerebroventricular injection of either 3mul Tris solution or 3microgram leptin, and a single intraperitoneal injection of either 2mul saline or 2microgram/kg sulfated CCK-8. The changes of the Fos expression were investigated in the paraventricular nucleus (Pa), retrochiasmatic area (RCh), lateral hypothalamic nucleus (LH), central nucleus of amygdala(Ce), supraoptic nucleus (SO), arcuate nucleus (Arc), ventromedial hypothalamic nucleus(VMH),dorsomedial hypothalamic nucleus (DM), ventral premammillary nucleus (PMV), superior lateral subdivision of parabrachial nucleus (LPBS), external lateral subdivision of parabrachial nucleus (LPBE), supragenual nucleus (SGe), area postrema (AP), medial area (SolM) and commissural area (SolC) of nucleus of the solitary tract nuclei. RESULTS: CCK increased the Fos expression in the Pa, RCh, LH, Ce, SO, Arc, VMH, DM, PMV, LPBS, LPBE and SolM. Leptin increased the Fos expression in the Pa, RCh, LH, SO, Arc, VMH, DM, PMV, LPBS, LPBE, SGe, AP and SolM. Injections of leptin and CCK significantly enhanced the Fos expression in the Pa, RCh, VMH, DM, LPBS, and SolM compared with those induced by leptin or CCK alone. CONCLUSION: Our results suggest that the Pa, RCh, VMH, DM, LPBS and SolM may be essential sites mediating the synergistic effect of leptin and CCK to regulate food intake.