Ontogeny of cholecystokinin-8-containing neuron system of the rat: an immunohistochemical analysis. I. Forebrain and upper brainstem.

Ontogeny of the cholecystokinin-8 (CCK) neuron system in the forebrain and upper brainstem of the rat was investigated by means of indirect immunofluorescence. CCK cells and fibers first appeared in the developing ventral tegmental area and in the primordium of the medial forebrain bundle, respectively, at gestational day 15 (12-14-mm embryos). From that time, CCK cells appeared in various areas of the forebrain and upper brainstem until birth and reached the maximum content at postnatal day 10. After postnatal day 10, although CCK cells tended to decrease slightly in number, colchicine treatment in the adult rats brought out numerous CCK cells in the same areas. In contrast, although CCK fibers developed only slightly during the fetal period, marked development was seen after birth, particularly between postnatal days 5 and 10. After that time, as the rats grew, CCK fibers continued to increase in number and formed a meshwork of varying density in various areas of the forebrain and upper brainstem.