Central dopaminergic neurons: Neurophysiological identification and responses to drugs

Neurons in the rat brain identified as dopaminergic were found to be remarkably homogeneous with respect to their firing pattern, and responses to drugs and other substances administered systemically, or applied iontophoretically.

Abstract

This chapter surveys and synthesizes the adaptive responses to the neuroleptic drugs that may bear on the mechanisms underlying the late and persistent or tardive dyskinesias associated with their use in the treatment of patients with severe chronic neuropsychiatric illnesses. The chapter provides an overview of the current use of the neuroleptic drugs, their neurological side effects, and their currently suspected mechanisms of action. There is a need for carefully controlled neuropathologic studies in animals and man following prolonged exposure to neuroleptic agents, using classical neurohistology and newer techniques such as chemical assays of transmitters and their metabolites, as well as biochemical and immunohistologic assays of neuron-specific enzymes, and the new labeling assays for neurotransmitter and drug receptors. Such methods are applicable to postmortem human brain tissue for a more direct evaluation of the current pathophysiologic hypotheses concerning the response of the brain to prolonged exposure to neuroleptic drugs, and the development of tardive dyskinesia. The precise pathophysiology of tardive dyskinesia remains uncertain. The study of neurological, behavioral, and endocrinological effects of the neuroleptic agents on the CNS has contributed to an improved understanding of their actions, which is at least equal to that of many other drugs used in medicine.