NT79

A novel neurotensin analog with selective behavioral effects

Mona Boules, Yanqi Liang, Siobhan Briody, Tomofumi Miura, Irfan Fauq, Alfredo Oliveros, Mina Wilson, Shaheen Khaniyev, Katrina Williams, Zhimin Li, Yanfei Qi, Michael Katovich, Elliott Richelson

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Neurotensin, a tridecapeptide, is widely distributed in the brain and gastrointestinal tract. It possesses analgesic, hypothermic, and antipsychotic-like properties. Neurotensin's effects are mediated mainly through two receptor subtypes, NTS1 and NTS2. Activation of NTS1 has been implicated in most of the pharmacological effects of neurotensin but is associated with hypothermia and hypotension. We report on a novel neurotensin analog with higher selectivity to NTS2, namely, NT79, which exhibits selective behavioral effects. NT79 was tested in animal models for pain (thermal-hot plate test; visceral-acetic acid-induced writhing test), and in animal models that are predictive of antipsychotic-like effects (apomorphine-induced climbing; d-amphetamine-induced hyperactivity; disruption of prepulse inhibition). Its effects on body temperature and on blood pressure were also determined. Neurochemical changes in extracellular neurotransmitters were measured using in vivo microdialysis while the rats were simultaneously evaluated for acetic acid-induced writhing with and without pretreatment with NT79. Binding data at molecularly cloned hNTS1 and hNTS2 suggest selectivity for hNTS2. NT79 blocked the acetic acid-induced writhing with an ED50 of 0.14 μg/kg while having no effect on thermal nociception. The writhing was paralleled by an increase in 5-HT which was attenuated by NT79. NT79 demonstrated antipsychotic-like effects by blocking apomorphine-induced climbing, d-amphetamine-induced hyperactivity, and reducing d-amphetamine- and DOI-induced disruption of prepulse inhibition. Uniquely, it caused no significant hypothermia and was without effect on blood pressure. NT79, with its higher selectivity to NTS2, may be potentially useful to treat visceral pain, and psychosis without concomitant side effects of hypothermia or hypotension.

Original languageEnglish
Pages (from-to)35-46
Number of pages12
JournalBrain Research
Volume1308
DOIs
Publication statusPublished - Jan 13 2010

Fingerprint

Neurotensin
Dextroamphetamine
Hypothermia
Acetic Acid
Antipsychotic Agents
Apomorphine
Hypotension
Animal Models
Hot Temperature
Visceral Pain
Blood Pressure
Nociception
Microdialysis
Body Temperature
Psychotic Disorders
Neurotransmitter Agents
Analgesics
Gastrointestinal Tract
Serotonin
Pharmacology

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

Cite this

Boules, M., Liang, Y., Briody, S., Miura, T., Fauq, I., Oliveros, A., ... Richelson, E. (2010). NT79: A novel neurotensin analog with selective behavioral effects. Brain Research, 1308, 35-46. https://doi.org/10.1016/j.brainres.2009.10.050

NT79 : A novel neurotensin analog with selective behavioral effects. / Boules, Mona; Liang, Yanqi; Briody, Siobhan; Miura, Tomofumi; Fauq, Irfan; Oliveros, Alfredo; Wilson, Mina; Khaniyev, Shaheen; Williams, Katrina; Li, Zhimin; Qi, Yanfei; Katovich, Michael; Richelson, Elliott.

In: Brain Research, Vol. 1308, 13.01.2010, p. 35-46.

Research output: Contribution to journalArticle

Boules, M, Liang, Y, Briody, S, Miura, T, Fauq, I, Oliveros, A, Wilson, M, Khaniyev, S, Williams, K, Li, Z, Qi, Y, Katovich, M & Richelson, E 2010, 'NT79: A novel neurotensin analog with selective behavioral effects', Brain Research, vol. 1308, pp. 35-46. https://doi.org/10.1016/j.brainres.2009.10.050
Boules M, Liang Y, Briody S, Miura T, Fauq I, Oliveros A et al. NT79: A novel neurotensin analog with selective behavioral effects. Brain Research. 2010 Jan 13;1308:35-46. https://doi.org/10.1016/j.brainres.2009.10.050
Boules, Mona ; Liang, Yanqi ; Briody, Siobhan ; Miura, Tomofumi ; Fauq, Irfan ; Oliveros, Alfredo ; Wilson, Mina ; Khaniyev, Shaheen ; Williams, Katrina ; Li, Zhimin ; Qi, Yanfei ; Katovich, Michael ; Richelson, Elliott. / NT79 : A novel neurotensin analog with selective behavioral effects. In: Brain Research. 2010 ; Vol. 1308. pp. 35-46.
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