Effect of peripheral cholecystokinin receptor agonists on c-Fos expression in brain sites mediating food consumption in rats

Peripheral cholecystokinin (CCK) elicits satiety by acting on hypothalamic nuclei. The anoretic effect of CCK is mediated by the vagus nerve and involves brainstem areas receiving vagal inputs, such as the nucleus tractus solitarius (NTS) and the area postrema (AP). This work aims to analyze, by measuring c-Fos expression, the effect of selective CCK receptor agonists on brain areas involved in foodintake/satiety process. We observed that SR-146,131, a CCK1R agonist, increased c-Fos expression in NTS and AP as well as in some hypothalamic nuclei. CCK-4, a CCK2R agonist which does not cross the blood-brain barrier (BBB), only was effective in the hypothalamus. Our data show that the activation of the brainstem is not a requisite to obtain a hypothalamic effect of peripheral CCK and suggest that CCK-4 may indirectly stimulate hypothalamic areas endowed with BBB, without previous activation of neither NTS nor AP. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.