Central dopamine-peptide interactions: Electrophysiological studies

Abstract

A variety of peptides have been shown to have physiological activity, either pre- or post-synaptically in DA systems. Significantly, this has not been true of all the peptides tested and physiological activity has for the most part, correlated with anatomical evidence for the presence of that peptide in the same area as DA and with the presence of specific receptors for the active peptide. In the main, biochemical and behavioral studies of the effects of peptides on the function of DA systems also correlate well with the effects of the various peptides on the activity of DA neurons. However, despite this growing body of knowledge we still know very little about the physiological relevance of most peptides to animal behavior or the interaction between these peptides and DA systems. This is due, in part, to the fact that the functioning of peptide systems is still relatively difficult to study in terms of synthesis, release, metabolism and turnover. The fact that there are very few selective non-peptide antagonists for many of these substances has also hampered the study of their function in the brain. Nevertheless, their proven interaction with midbrain DA systems, regardless of whatever else they may do in the brain, makes them of great potential clinical interest. Given the number of neurological and mental disorders in which malfunction of the DA system is presumed to be involved, any endogenous substance that can modulate activity of the DA cells and thus provide a new mechanism for controlling the functioning of central DA systems may have potential therapeutic value. Furthermore, in many of the CNS disorders in which DA systems are thought to be involved a change in the concentration (in dopamine-containing areas) of one or more of the peptides reviewed here has been found. Such findings provide further support for the idea that these substances and their interaction with dopamine systems may turn out to be clinically relevant.