Alteration of thermoregulatory set point with opioid agonists

This paper focuses on the behavioral thermoregulatory effects of i.c.v. administration of [D-Ala²-MePhe⁴,Gly⁵-ol]enkephalin (DAMGO), cyclic [D-Pen²,D-Pen⁵]enkephalin (DPDPE) and U-50,488H, selective agonists for the mu, delta and kappa opioid receptors, respectively. Rats were tested in a thermally graded tunnel (thermocline) which allowed for simultaneous measurement of body temperature, ambient temperature selection and general ambulatory activity levels. DAMGO (0.3 μg) caused an increase in body temperature which was facilitated by the selection of a warm ambient temperature. Both DPDPE (30 μg) and U-50,488H (100 μg) caused decreases in body temperature which were accompanied by a selection of a cool ambient temperature. In each case there was evidence for a regulated change in body temperature, with DAMGO increasing thermoregulatory set point and DPDPE and U-50,488H decreasing set point. DAMGO and U-50,488H produced a depression of activity levels for the first 15 min after injection. DAMGO and DPDPE produced increases in activity levels which peaked after body temperature had returned toward base-line levels. These data characterize further the differentiable profiles of physiological effects produced by these three compounds. The central modulation of the control of body temperature by these opioid receptor agonists may reflect a role of endogenous opioids in thermoregulatory control.