Neurotensin: Perchance an endogenous neuroleptic?

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Neurotensin (NT), an endogenous tridecapeptide, is distributed heterogeneously in brain, localized preferentially in the synaptosomal fraction after density gradient centrifugation and binds to brain membranes reversibly, saturably, and with high affinity. These characteristics along with the demonstration of a Ca++-dependent release of this neuropeptide from brain slices suggest that this substance is a neuromodulator. The present work sought to compare certain properties of NT with neuroleptic agents since preliminary studies suggested similarities between the peptide and antipsychotic drugs and furthermore NT is localized in high concentration in the nucleus accumbens, a major site of termination of the mesolimbic dopamine (DA) system, a circuit implicated in the pathogenesis of schizophrenia. Like neuroleptics NT injected intracisternally (IC) or intracerebroventricularly (but not peripherally) produces: (i) potentiation of barbiturate sedation, (ii) hypothermia, (iii) diminished locomotor activity, and (iv) muscle relaxation. Treatments which reduce the functional activity of DA circuits (6-hydroxydopamine-induced DA depletion or haloperidol pretreatment) augment NT-induced hypothermia. In addition, bilateral nucleus accumbens injections of NT, like haloperidol, significantly antagonized increased locomotor activity and rearing induced by d-amphetamine (2 mg/kg ip). The hypothermia and muscle relaxation induced by both NT and neuroleptics is antagonized by IC injection of thyrotropin-releasing hormone, the endogenous tripeptide. Unlike neuroleptic drugs, NT did not inhibit the binding of 3H-spiroperidol to the DA receptors in either the nucleus caudatus or the nucleus accumbens. NT, as previously reported, was found to be a potent antinociceptive agent. It was more potent on a molar basis than met-enkephalin, leu-enkephalin, and morphine but less potent than β-endorphin. These findings, taken together, support the hypothesis that NT is a neuromodulator. It is a neuropeptide which shares many but not all properties with neuroleptic agents. Its role in normal and abnormal behavioral and neurological disease states remains undetermined.

Original languageEnglish (US)
Pages (from-to)283-302
Number of pages20
JournalBiological Psychiatry
Issue number2
StatePublished - Jan 1 1980
Externally publishedYes

ASJC Scopus subject areas

  • Biological Psychiatry


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