The interaction of neurotensin with dopaminergic pathways in the central nervous system: basic neurobiology and implications for the pathogenesis and treatment of schizophrenia

This chapter summarizes the available data supporting a neuroregulatory role for neurotensin (NT) in the mammalian central nervous system (CNS). The major focus is on effects of centrally administered NT, and a secondary focus is the possible importance of this peptide in the pathophysiology of schizophrenia and in the mechanism of action of antipsychotic drugs.

The Neurobiology of Neurotensin

The Fifth Annual Washington Spring Symposium on Health Sciences attracted over 400 scientists from 20 countries. It was held at the Lisner Auditorium of the George Washington University in Washington. D.C. The theme of the meeting was neural and endocrine peptides and receptors. The meeting emphasized basic and clinical research on neural and endocrine peptides and receptors. The six plenary sessions emphasized pituitary peptides, releasing factors, brain peptides, growth factors, peripheral peptides, and clinical applications. The chapters in this volume are derived from each of these six scientific sessions plus the poster and special sessions. The Abraham White Distinguished Scientist A ward was presented to Dr. Julius Axelrod for his numerous contributions to the field of neurochemistry. He presented the keynote address, which was entitled "The Regulation of the Release of ACTH." Dr. Axelrod discussed numerous factors, such as the peptides CRF, VIP, and somatostatin, that regulate hormone secretion from pituitary cells. The Distinguished Public Service Award was presented to Senator Lowell Weicker, Jr., in recognition of his leadership and outstanding achievements in the United States Senate and for his legislative support for biomedical research and education. In the symposium banquet address, Senator Weicker stressed the need for continued federal support of biomedical science research.

Neural and Endocrine Peptides and Receptors

Centrally administered neurotensin suppresses locomotor hyperactivity induced by d-amphetamine but not by scopolamine or caffeine.

Behavioral effects of neurotensin in the open field: structure-activity studies

The emphasis of this chapter is on the mechanisms and functional significance of the interaction of neuropeptides with the putative neurotransmitter dopamine in the central nervous system (CNS). Accumulating evidence supports the contention that these interactions are of physiological importance and have added a novel dimension to our concepts of the pathophysiology of psychiatric disorders and the mechanisms of psychotropic drug action. Primary emphasis has been placed on findings from our laboratories and those of others concerning interactions between the tridecapeptide neurotensin (NT) and dopamine neurons. Where appropriate, the influence of other neuropeptides on dopamine mechanisms are discussed. We (Nemeroff et al., 1982a, 1983a, 1984) and others (Goedert, 1984) have previously reviewed the neuropharmacological, neuroanatomical and neurochemical literature supporting a functional interaction between NT-containing and dopamine-containing cells in the CNS and the interested reader is referred to these articles for a more comprehensive review than is intended here. The major objective of this chapter is to integrate recent data concerning the molecular basis of NT-dopamine interactions into the developing concept of the functional significance of such interactions.

K. M. Skoog

Papers

Neuropeptide-Dopamine Interactions: Focus on Neurotensin