Neurotensin analog NT77 induces regulated hypothermia in the rat

Christopher J. Gordon, Beth McMahon, Elliott Richelson, Beth Padnos, Laurence Katz

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Abstract

The potential use of hypothermia as a therapeutic treatment for stroke and other pathological insults has prompted the search for drugs that can lower core temperature. Ideally, a drug is needed that reduces the set-point for control of core temperature (Tc) and thereby induces a regulated reduction in Tc. To this end, a neurotensin analog (NT77) that crosses the blood brain barrier and induces hypothermia was assessed for its effects on the set-point for temperature regulation in the Sprague-Dawley rat by measuring behavioral and autonomic thermoregulatory responses. Following surgical implanation of radiotransmitters to monitor Tc, rats were placed in a temperature gradient and allowed to select from a range of ambient temperatures (Ta) while Tc was monitored by radiotelemetry. There was an abrupt decrease in selected Ta from 29 to 16°C and a concomitant reduction in Tc from 37.4 to 34. 0°C 1 hr after IP injection of 5.0 mg/kg NT77. Selected Ta and Tc then recovered to control levels by 1.5 hr and 4 hr, respectively. Oxygen consumption (M) and heat loss (H) were measured in telemetered rats housed in a direct calorimeter maintained at a Ta of 23.5°C. Injection of NT77 initially led to a reduction in M, little change in H, and marked decrease in Tc. H initially rose but decreased around the time of the maximal decrease in Tc. Overall, NT77 appears to induce a regulated hypothermic response because the decrease in Tc was preceded by a reduction in heat production, no change in heat loss, and preference for cold Ta's. Inducing a regulated hypothermic response with drugs such as NT77 may be an important therapy for ischemic disease and other insults.

Original languageEnglish (US)
Pages (from-to)2611-2623
Number of pages13
JournalLife Sciences
Volume73
Issue number20
DOIs
StatePublished - Oct 3 2003

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Keywords

  • Behavioral thermoregulation
  • Ischemic disease
  • Neuropeptide
  • Temperature regulation

ASJC Scopus subject areas

  • Pharmacology

Cite this

Gordon, C. J., McMahon, B., Richelson, E., Padnos, B., & Katz, L. (2003). Neurotensin analog NT77 induces regulated hypothermia in the rat. Life Sciences, 73(20), 2611-2623. https://doi.org/10.1016/S0024-3205(03)00663-5