Journal article
Neurotensin analog selective for hypothermia over antinociception and exhibiting atypical neuroleptic-like properties
Brain research, v 919(1), pp 1-11
16 Nov 2001
PMID: 11689157
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Neurotensin (NT) is a tridecapeptide neurotransmitter in the central nervous system. It has been implicated in the therapeutic effects of neuroleptics. Central activity of NT can only be demonstrated by direct injection into the brain, since it is readily degraded by peptidases in the periphery. We have developed many NT(8–13) analogs that are resistant to peptidase degradation and can cross the blood–brain barrier (BBB). In this study, we report on one of these analogs, NT77L. NT77L induced hypothermia (ED
50=6.5 mg/kg, i.p.) but induced analgesia only at the highest dose examined (20 mg/kg, i.p.). Like the atypical neuroleptic clozapine, NT77L blocked the climbing behavior in rats induced by the dopamine agonist apomorphine (600 μg/kg) with an ED
50 of 5.6 mg/kg (i.p.), without affecting the licking and the sniffing behaviors. By itself NT77L did not cause catalepsy, but it moderately reversed haloperidol-induced catalepsy with an ED
50 of 6.0 mg/kg (i.p.). Haloperidol alone did not lower body temperature, but it potentiated the body temperature lowering effect of NT77L. In studies using in vivo microdialysis NT77L showed similar effects on dopamine turnover to those of clozapine, and significantly different from those of haloperidol in the striatum. In the prefrontal cortex, NT77L significantly increased serotonergic transmission as evidenced by increased 5-hydroxyindole acetic acid:5-hydroxytryptamine (5-HIAA:5-HT) ratio. Thus, NT77L selectively caused hypothermia, over antinociception, while exhibiting atypical neuroleptic-like effects.
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Details
- Title
- Neurotensin analog selective for hypothermia over antinociception and exhibiting atypical neuroleptic-like properties
- Creators
- Mona Boules - Mayo ClinicBeth McMahon - Mayo ClinicLewis Warrington - Mayo ClinicJennifer Stewart - Mayo ClinicJoshua Jackson - Mayo ClinicAbdul Fauq - Mayo ClinicDaniel McCormick - Mayo ClinicElliott Richelson - Mayo Clinic
- Publication Details
- Brain research, v 919(1), pp 1-11
- Publisher
- Elsevier
- Number of pages
- 11
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000172302300001
- Scopus ID
- 2-s2.0-0035900186
- Other Identifier
- 991021900016504721
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InCites Highlights
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- Web of Science research areas
- Neurosciences