Elsevier

Regulatory Peptides

Volume 36, Issue 2, 29 October 1991, Pages 153-164
Regulatory Peptides

Review
The neurobiology of neurotensin: focus on neurotensin-dopamine interactions

https://doi.org/10.1016/0167-0115(91)90053-JGet rights and content

Abstract

Neurotensin (NT) is a tridecapeptide which fulfills many of the requisite criteria for a role as a central nervous system (CNS) neurotransmitter. It is closely associated with CNS dopamine neurons and has been shown to interact with dopamine at physiological, anatomical and behavioral levels. Neurotensin is colocalized with dopaminergic neurons in the hypothalamus and midbrain. In addition, it blocks behaviors associated with activation of the dopaminergic pathways. Centrally administered NT has been shown to mimic many of the actions of antipsychotic drugs. In addition, the concentration of NT in cerebrospinal fluid is decreased in patients with schizophrenia. Administration of clinically effective antipsychotic drugs increases concentrations of NT in the caudate nucleus and nucleus accumbens. NT has been shown to play a role in signal transduction by mostly mobilizing calcium stores following inosital phosphate formation. This has been linked to subsequent events in protein phosphorylation. Lipophillic NT receptor agonists may represent a novel approach to the development of a new class of antipsychotic drugs.

References (88)

  • K. Tanaka et al.

    Structure and functional expression of the cloned rat neurotensin receptor

    Neuron

    (1990)
  • P. Kitabgi et al.

    Two populations of neurotensin binding sites in murine brain: discrimination by the antihistamine levocabastine reveals a markedly different radioautographic distribution

    Eur. J. Pharmacol.

    (1987)
  • P.C. Emson et al.

    Neurotensin in human brain: regional distribution and effects of neurological illness

    Brain Res.

    (1985)
  • L.H. Lazarus et al.

    Distribution, localization and characterization of neurotensin binding sites in the rat brain

    Neuropharmacology

    (1977)
  • W.S. Young et al.

    Neurotensin receptor localization by light microscopic autoradiography in rat brain

    Brain Res.

    (1981)
  • R. Quirion et al.

    Comparative localization of neurotensin receptors in nigrostriatal and mesolimbic dopaminergic terminals

    Brain Res.

    (1985)
  • M. Goedert et al.

    Neurotensin stimulates inositol phospholipid hydrolysis in rat brain slices

    Brain Res.

    (1984)
  • K.S. Kanba et al.

    Comparison of the stimulation of inositol phospholipid hydrolysis and of cyclic GMP formation by neurotensin, some of its analogs and neuromedin in neurblastoma clone N1E115

    Biochem. Pharmacol.

    (1987)
  • J.M. Studler et al.

    Extensive co-localization of neurotensin with dopamine in rat meso-cortico-frontal dopaminergic neurons

    Neuropeptides

    (1988)
  • R. Miyoshi et al.

    Modulation of dopamine D receptor binding by neurotensin in the rat striatum

    Neurochem. Int.

    (1989)
  • V. Seutin et al.

    Electrophysiological effects of neurotensin on dopaminergic neurons of the ventral tegmental area of the rat in vitro

    Neuropharmacology

    (1989)
  • M.S. Starr

    Influence of peptides on [3H]dopamine release from superfused rat striatal slices

    Neurochem. Int.

    (1982)
  • R.D. Myers et al.

    Neurotensin perfusion of rat hypothalamus: dissociation of dopamine release from body temperature change

    Neuroscience

    (1984)
  • C.D. Blaha et al.

    Effects of neurotensin on dopamine release and metabolism in the rat striatum and nucleus accumbens. Cross validation using in vivo voltammetry and microdialysis

    Neuroscience

    (1990)
  • P.W. Kalivas et al.

    Behavioral and neurochemical effects of daily injections with neurotensin into the ventral tegmental area

    Brain Res.

    (1985)
  • P.W. Kalivas et al.

    Increase in spontaneous motor activity following infusion of neurotensin into the ventral tegmental area

    Brain Res.

    (1981)
  • P.W. Kalivas et al.

    Behavioral and neurochemical effects of neurotensin microinjection into the ventral tegmental area of the rat

    Neuroscience

    (1983)
  • P.W. Kalivas et al.

    Neuroanatomical site specific modulation of spontaneous motor activity by neurotensin

    Eur. J. Pharmacol.

    (1982)
  • K.M. Skoog et al.

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

    Neuropharmacology

    (1986)
  • A.J. Osbahr et al.

    Centrally administered neurotensin: activity in the Jolou-Couvoisier muscle relaxation test in mice

    Eur. J. Pharmacol.

    (1979)
  • D. Luttinger et al.

    The effects of neuropeptides on discrete trial conditioned avoidance responding

    Brain Res.

    (1982)
  • J.M. Radke et al.

    Effects of short- and long-term haloperidol administration and withdrawal on regional brain cholecystokinin and neurotensin concentrations in the rat

    Brain Res.

    (1989)
  • B. Levant et al.

    Effects of anticholinergic drugs on regional neurotensin concentrations

    Eur. Pharmacol.

    (1989)
  • C.D. Kilts et al.

    Differential effects of antipsychotic drugs on the neurotensin content of discrete rat brain nuclei

    Biochem. Pharmacol.

    (1988)
  • K.M. Merchant et al.

    Haloperidol rapidly increases the number of neurotensin mRNA-expressing neurons in neostriatum of the rat brain

    Brain Res.

    (1991)
  • K.M. Merchant et al.

    Effects of amphetamine analogs on neurotensin concentrations in rat brain

    Eur. J. Pharmacol.

    (1987)
  • L.H. Lindstrom et al.

    Reduced CSF neurotensin concentrations in drug-free schizophrenic patients

    Schizophrenia Res.

    (1988)
  • C.B. Nemeroff et al.

    Neurotensin-dopamine interactions in the CNS

    Trends Pharmacol. Sci.

    (1985)
  • B. Levant et al.

    The psychobiology of neurotensin

  • M.H. Fernstrom et al.

    Neurotensin

  • S.E. Leeman et al.

    Neurotensin, discovery, isolation, characterization, synthesis and possible physiological roles

    Ann. N.Y. Acad. Sci.

    (1982)
  • P.J. Manberg et al.

    Regional distribution of neurotensin in human brain

    J. Neurochem.

    (1982)
  • M.J. Alexander et al.

    Distribution of neurotensin/neuromedinN mRNA in rat forebrain: unexpected abundance in hippocampus and subiculum

  • G.R. Uhl et al.

    Regional and subcellular distribution of brain neurotensin

    Life Sci.

    (1977)
  • Cited by (0)

    View full text