Cholecystokinin induces Fos expression in the brain of the Japanese quail.

Systemic administration of cholecystokinin (CCK) inhibits feeding in birds. However, the signaling pathway through which CCK induces this effect is unknown, and its role as a natural satiety signal is controversial. To address these issues, we used immunocytochemistry for the immediate-early gene protein Fos to localize sites of neuronal activation in the brain of Japanese quail (Coturnix japonica) after CCK treatment. Food intake was inhibited in a dose-dependent manner following intraperitonal (i.p.) injection of CCK, with an effective dose range of 1-50 micrograms/kg. To test the hypothesis that CCK induces a distinct pattern of Fos-like immunoreactivity (FLI) in the brain, we compared FLI in birds given CCK (20 micrograms/kg, i.p.) with that in birds given a nonspecific chemical inhibitor of feeding, lithium chloride (LiCl, 40 mg/kg, i.p.), at doses that reduce feeding to a similar level (30% of saline controls). FLI-positive cell nuclei were counted in 14 brain regions after administration of CCK, LiCl, or saline. CCK uniquely induced FLI in the paraventricular, infundibular, periventricular hypothalamic, and medial mamillary nuclei of the hypothalamus. However, CCK and LiCl both induced a comparable pattern of FLI in the hindbrain, with strong staining in the nucleus of the solitary tract and dorsal motor nucleus of the vagus. These findings demonstrate the ability of CCK to activate the central nervous system in birds and suggest that the peptide exerts specific actions in the hypothalamus. However, the possibility that the FLI observed may have arisen through nonspecific effects of CCK on gastrointestinal physiology cannot be discounted.