Subfornical organ: a novel site for the actions of cholecystokinin

Abstract

The subfornical organ (SFO) is an important sensory circumventricular organ implicated in the regulation of fluid homeostasis and energy balance. We examined the response of SFO neurons to cholecystokinin (CCK) using the functional activation markers c‐Fos and p‐ERK. The number of c‐Fos and p‐ ERK immunoreactive SFO neurons were determined in 18 hr‐fasted rats in response to vehicle, CCK (16μg/kg, i.p.) alone or CCK in combination with a CCK1 or a CCK2 receptor antagonist (Devazepide; 600 μg/kg and L‐365,120 [L‐365]; 100 μg/kg, respectively). The nucleus of the solitary tract (NTS) was used as a positive control region for CCK‐induced activity. After 90 min, CCK induced a significant increase in the number of c‐Fos neurons in the NTS (259.2±20.8) compared to vehicle (47.5±2.5). Similarly, in the SFO, c‐Fos was expressed in 40.5 ± 10.6 neurons in CCK‐treated compared to 6.6 ±2.7 in vehicle‐treated rats (n=4/group). Devazepide significantly reduced the effects of CCK in the NTS but not in SFO. L‐365 blocked the effects of CCK in both regions. After 15 min, CCK increased the number of p‐ERK neurons in NTS (27.0±4.0) as well as SFO (18.0±4.0) compared to vehicle (8.0 ±2.6 and 4.3±0.6 respectively). Both devazepide and L‐365 reduced CCK induced p‐ERK in NTS, but only L‐365 reduced it in the SFO. In conclusion, SFO represents a novel CNS site at which circulating CCK may act to influence autonomic control centers in the hypothalamus.