Effect of mu-, kappa-, and delta-selective opioid agonists on thermoregulation in the rat.
Level 5 - mechanism / opinion, no new human data
Animal research
PubMed 1361992 · doi:10.1016/0091-3057(92)90504-9
What was done
Researchers evaluated the effects of intracerebroventricular administration of selective opioid receptor agonists on brain surface temperature, oxygen consumption, and heat exchange in unrestrained male Sprague-Dawley rats using whole-body calorimetry. Tested agonists included PL-017 (mu-selective), dynorphin A1-17 (kappa-selective), and DPDPE (delta-selective), with specificity tested using antagonist pretreatment (CTAP for mu, nor-binaltorphimine for kappa).
What was found
Intracerebroventricular injection of PL-017 (1.86 nM) produced hyperthermia through increased oxygen consumption and reduced heat exchange during the first 15 to 45 minutes post-injection, which was abolished by CTAP (0.75 nM). Dynorphin A1-17 (4.65 nM) reduced both oxygen consumption and heat exchange, resulting in hypothermia that was blocked by nor-binaltorphimine (25 nM). DPDPE (4.64 nM) caused no significant changes in brain surface temperature, oxygen consumption, or heat exchange. Exact numerical values and variances for temperature and metabolic rates were not reported in the abstract.
Why it matters
This study demonstrates that central mu- and kappa-opioid receptors bidirectionally regulate body temperature through distinct combined effects on oxidative metabolism and heat loss mechanisms.
Limits
The study was conducted in male rats, limiting generalizability to females and humans. Sample size, control group details, and quantitative values for temperature and metabolic changes were not provided in the abstract.
Cited by
- supports Heat stress in rats increases endogenous dynorphin expression in the brain.