The colocalization of cholecystokinin and tyrosine hydroxylase mRNAs in mesencephalic dopaminergic neurons in the rat brain examined by in situ hybridization.

The colocalization of cholecystokinin and tyrosine hydroxylase mRNAs was studied with a cellular resolution in the mesencephalic dopaminergic neurons of the rat brain by in situ hybridization using synthetic oligonucleotides. An extensive colocalization of cholecystokinin-expressing cells, greater than that seen previously by immunohistochemistry, was found in the ventral tegmental area and in the substantia nigra pars compacta. We observed in these regions that cholecystokinin and tyrosine hydroxylase mRNAs coexisted in the same neurons but not all dopamine cells expressed cholecystokinin mRNA. 6-Hydroxydopamine-induced destruction of mesostriatal dopaminergic neurons resulted in a complete loss of cholecystokinin and tyrosine hydroxylase mRNA expression throughout the substantia nigra pars compacta, indicating that all cholecystokinin expressing cells are 6-hydroxydopamine-sensitive. While increased enkephalin mRNA expression in the striatum ipsilateral to the lesion was detected, no change of cholecystokinin mRNA expression was observed in any forebrain on the lesioned side, suggesting that cholecystokinin expression in the forebrain is not under dopaminergic control. These results show the usefulness of the in situ hybridization approach for the precise localization of cells in rat brain which express mRNAs for cholecystokinin and tyrosine hydroxylase and for the study of the effects of neurotoxic lesions on these cells.