Related Experiment Video
Updated: Aug 17, 2026
Short-Duration Hypothermia Induction in Rats using Models for Studies examining Clinical Relevance and Mechanisms
Published on: March 3, 2021
Brain delta2 opioid receptors mediate SNC-80-evoked hypothermia in rats
Scott Manning Rawls1, Jennifer Marie Hewson, Saadet Inan
1Department of Pharmaceutical Sciences, Temple University School of Pharmacy, 3307 North Broad Street, Philadelphia, PA 19140, USA. scott.rawls@temple.edu
Abstract:
Despite insights into an increasingly significant role for delta opioid receptors in thermoregulation, it is unclear whether delta receptors located in the brain or periphery play the more critical role in body temperature regulation. Moreover, it is not entirely clear which delta receptor phenotype, delta1 or delta2, mediates the hypothermic actions of delta agonists. Because SNC-80 distributes into central and peripheral compartments and produces rapid hypothermia following systemic injection, the nonpeptide delta agonist is particularly useful in discriminating the site of action of delta receptor-mediated hypothermia. To determine the locus and phenotype of delta receptor which mediates SNC-80-induced hypothermia, we injected SNC-80 and phenotype selective delta antagonists to male Sprague-Dawley rats. SNC-80 (10-50 mg/kg, im) evoked hypothermia that peaked 30 min post-injection. Naltrexone (5 mg/kg, sc), an opioid antagonist, or naltrindole (5 mg/kg, sc), a delta antagonist, blocked the hypothermic response to SNC-80 (35 mg/kg, im). The hypothermia caused by SNC-80 (35 mg/kg, im) was blocked by a delta2 antagonist, naltriben (2.5 mg/kg, sc), but was not affected by BNTX (5 and 10 mg/kg, sc), a delta1 antagonist. The administration of naltriben (10 microg/rat, icv) 30 min before SNC-80 (35 mg/kg, im) prevented SNC-80-evoked hypothermia. In contrast, methylnaltrexone (5 mg/kg, sc), a peripherally restricted opioid antagonist, did not affect the hypothermia caused by SNC-80. The present data demonstrate that selective activation of brain delta2 receptors is a major mechanism of SNC-80-evoked hypothermia in rats.
Insights
Brain delta2 opioid receptors, not peripheral ones, primarily mediate SNC-80-induced hypothermia. This study identifies delta2 receptors as key players in body temperature regulation via delta agonists.
Area of Science:
- Neuroscience
- Pharmacology
- Physiology
Background:
- Delta opioid receptors play a significant role in thermoregulation.
- The specific location (central vs. peripheral) and subtype (delta1 vs. delta2) of delta receptors mediating hypothermia are not fully understood.
Purpose of the Study:
- To determine the locus and receptor phenotype responsible for SNC-80-induced hypothermia.
- To investigate the role of central versus peripheral delta opioid receptors in body temperature regulation.
Main Methods:
- Male Sprague-Dawley rats were injected with SNC-80, a nonpeptide delta agonist, and selective delta antagonists.
- Antagonists included naltrexone, naltrindole, naltriben (delta2 antagonist), BNTX (delta1 antagonist), and methylnaltrexone (peripheral opioid antagonist).
- Central injections into the lateral ventricle (icv) were also performed.
Main Results:
- SNC-80 administration induced dose-dependent hypothermia.
- The hypothermic effect of SNC-80 was blocked by opioid and delta antagonists, as well as a delta2 antagonist (naltriben).
- A delta1 antagonist (BNTX) did not block the hypothermia, and a peripherally restricted antagonist (methylnaltrexone) had no effect.
- Central administration of naltriben prevented SNC-80-induced hypothermia.
Conclusions:
- Selective activation of brain delta2 opioid receptors is the primary mechanism underlying SNC-80-evoked hypothermia.
- These findings highlight the critical role of central delta2 receptors in regulating body temperature.
