Hyperthermic response of the cat to intraventricular injection of the opioid delta-receptor agonist D-Ala²D-Leu⁵enkephalin

The δ opioid receptor agonist D-Ala²-D-Leu⁵-enkephalin was injected into the third cerebral ventricle of cats to determine its effects on core temperature for comparison with other peptide and non-peptide opioids that act on a variety of receptors to alter thermoregulation. Like other opioid peptides that have been studied in this species, D-Ala²-D-Leu⁵-enkephalin (5-25 μg) induced a dose-related hyperthermia. This response was undiminished in cats tolerant to morphine and was found to consist of two components. One component of the hyperthermic response was inhibited by pretreatment with low doses of opioid antagonists (25μg naloxone; 5-15μg naltrexone) and may be mediated by the v₂-receptor that mediates this response to D-Ala²-Met-enkephalinamide. The other component, which was prevented by 100μg naltrexone but still only partially inhibited by 250 μ naloxone, is attributed to δ-receptor stimulation. In tests over a range of environmental temperatures, the hyperthermic response to 10μg D-Ala²-D-Leu⁵-enkephalin was less in a 4°C environment than at the usual laboratory temperature of 22°C. Responses in 22 and 34°C environments were similar. No increase in respiratory rate occurred to indicate activation of compensatory heat-loss mechanisms so that the hyperthermia was indicative of an increase in the level about which body temperature is regulated.