Peptide-monoamine coexistence: Studies of the actions of cholecystokinin-like peptide on the electrical activity of midbrain dopamine neurons

Abstract

Recent studies have shown that a cholecystokinin-like peptide coexists in a subpopulation of midbrain dopamine-containing neurons. Using extracellular single unit recording techniques we have found that this peptide increases the activity of some, but not all, dopaminergic neurons (identified on the basis of their electrophysiological features). The responsive neurons were found exclusively in areas which were subsequently shown, using immunocytochemical techniques, to contain both cholecystokinin and the enzyme marker for dopaminergic neurons, tyrosine hydroxylase. When administered intravenously, cholecystokinin increased the firing rate of dopaminergic neurons lying in cholecystokinin-rich areas of the substantia nigra. Cells in cholecystokinin-rich ventral tegmental areas showed more variable responses to comparable doses of the peptide. Iontophoretically-applied cholecystokinin consistently activated dopaminergic cells in the substantia nigra and ventral tegmental area, increasing their firing rate and their bursting activity. Cholecystokinin increased the firing rate of some of those neurons to the extent that they were driven into apparent depolarization inactivation. Furthermore, iontophoresis of cholecystokinin resulted in an activation of a population of normally quiescent dopaminergic cells. These results are discussed in light of a possible functional role of cholecystokinin-like peptides in the brain dopaminergic systems. It is suggested that cells in the dopamine-rich areas of the mesencephalon can be characterized both on the basis of their content of peptide and/or catecholamine and of their responsiveness to cholecystokinin-like peptides.