EFFECT OF AMBIENT-TEMPERATURE ON THE ABILITY OF MU-SELECTIVE, KAPPA-SELECTIVE AND DELTA-SELECTIVE OPIOID AGONISTS TO MODULATE THERMOREGULATORY MECHANISMS IN THE RAT

Tyr-Pro-N-MePhe-D-Pro-NH2 (1.86 nmol), dynorphin A(1-17) (4.65 nmol) a nd DPDPE (4.64 nmol), which are selective for mu-, kappa- and delta- o pioid receptors, respectively, were injected into the right lateral ve ntricle of unrestrained male Sprague-Dawley rats. At ambient temperatu res of 30 degrees C and 5 degrees C, brain surface temperature (T-b), oxygen consumption (V-O2) and heat exchange (Q) were measured for 3 hr after injection in a gradient-layer calorimeter. Tyr-Pro-N-MePhe-D-Pr o-NH2 at 30 degrees C caused significant hyperthermia (1.39 +/- 0.48 d egrees C) with onset occurring 15 to 30 min after injection and lastin g 60 min after injection. Increased T-b was due to a significant decre ase in Q (-1.31 +/- 0.31 cal/g/hr) and to a 60 to 75% increase in V-O2 compared with saline controls. Thirty-min pretreatment with cyclic D- Phe-Cys-Tyr-D-Trp-Arg-Thr-PenThr-NH2 (0.74 nmol), a mu-selective antag onist, blocked the changes. At 30 degrees C, neither dynorphin A(1-17) nor DPDPE significantly altered T-b, Q or V-O2 At 5 degrees C ambient , Tyr-Pro-N-MePhe-D-Pro-NH2 decreased V-O2, resulting in hypothermia ( -1.01 degrees +/- 0.46 degrees C). Q was significantly reduced during the same period. Postinjection thermoregulatory responses to i.c.v. in jection of dynorphin A(1-17) at 5 degrees C varied widely from animal to animal, and lethality (33%, within 60 min after injection) became a significant factor. Dynorphin-induced hypothermia (-1.05 +/- 0.58 deg rees C) in the remainder of this group was blocked by nor-BNI (25 nmol , 15-min pretreatment), a kappa-selective antagonist. At 5 degrees C, T-b, Q and V-O2 were not significantly affected by central administrat ion of DPDPE. The delta-selective antagonist naltrindole (1 nmol, 15-m in pretreatment) had no effect of its own. We have demonstrated that c hanging the ambient temperature modifies the thermoregulatory effects of selective opioid agonists at their receptors.