Postprandial neuronal activation in the nucleus of the solitary tract is partly mediated by CCK-A receptors

CCK-A receptors and neurons of the nucleus of the solitary tract (NTS) are involved in the regulation of food intake, and in rats, there is evidence f or involvement of an intestinal vagal afferent pathway. Studies investigati ng the role of CCK-A receptors in activation of NTS neurons using highly se lective CCK-A receptor agonists and antagonists have yielded conflicting da ta. In the present study, we investigated CCK-induced and postprandial acti vation of NTS neurons, together with food intake studies, in CCK-A receptor -deficient Otsuka Long-Evans Tokushima fatty (OLETF) rats. Activated NTS ne urons were detected using immunohistological staining for c-Fos protein. Ex ogenous CCK increased the number of c-Fos protein-positive cells in the NTS of Sprague-Dawley and CCK-A receptor-intact Long-Evans Tokushima Otsuka (L ETO) rats but had no effect in CCK-A receptor-deficient OLETF rats. Food in take-induced c-Fos protein expression in NTS neurons was significantly redu ced in CCK-A receptor-deficient OLETF rats compared with Sprague-Dawley or LETO rats. Postprandial c-Fos protein expression in the NTS was also signif icantly decreased after pretreatment with the CCK-A receptor antagonist MK3 29 after both short- and long-term fasting periods. Exogenous CCK decreased cumulative food intake in Sprague-Dawley and LETO rats but not in OLETF ra ts. These data demonstrate that CCK-A receptors are involved in the CCK- an d food-induced c-Fos protein expression in the NTS. Taken together with the results of the food intake studies, this suggests that activation of CCK- A receptors is involved in the postprandial activation of NTS neurons and i n the regulation of food intake.