Interaction between opioid agonists and neurotensin on thermoregulation in the rat. I. Body temperature

To examine the role of neurotensin in opioid-induced thermo-regulation, Tyr-Pro-N-MePhe-D-Pro-NH2 (PL-017, 1.86 nmol i.c.v.), neurotensin (NT, 0.0747-2.98 nmol i.c.v.), ([trans-(+/-)-3, 4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]benzenacetamide+ ++]) (U50,488H; U50, 10-40 mg/kg s.c.), dynorphin A1-17 (DY, 4.65 nmol i.c.v.) and DPDPE (4.65 nmol i.c.v.) were injected alone or in combination with NT into unrestrained, male S-D rats. At 20 +/- 2 degrees C ambient, body temperature (Tb) was measured for 3 hr after injection. PL-017 induced dose-dependent hyperthermia; NT, DY and U50 produced dose-related hypothermia. NT (0.0747 nmol) had no effect on PL-017-induced hyperthermia; higher doses of PL-017/NT antagonized the hyperthermia and increased the peak and duration of the hypothermia. Pretreatment with cyclic D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP; 0.74 nmol i.c.v.) blocked the enhanced PL-017/NT-induced hypothermia but had no effect on NT-induced hypothermia. DY/NT reduced Tb dose dependently but the effect did not differ significantly from NT alone. U50 (20 or 40 mg/kg)/NT increased the peak and duration of the hypothermic response. Naloxone pretreatment (10 mg/kg s.c.) blocked the effect of U50 alone and in combination with NT, as did the peripheral opioid antagonist, naloxone methiodide (100 mg/kg s.c.). Nor-binaltorphimine (25 nmol i.c.v.) partially blocked the effect of U50 on Tb and had no effect on NT or U50/NT. DPDPE did not alter Tb alone or in combination with NT. The data presented provide information on the role of NT in opioid-induced thermoregulation.