INTERACTION BETWEEN OPIOID AGONISTS AND NEUROTENSIN ON THERMOREGULATION IN THE RAT .1. BODY-TEMPERATURE

To examine the role of neurotensin in opioid-induced thermoregulation, 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 A(1-17) (DY, 4.65 nmol i.c.v,) and DPDPE (4.65 nm ol i.c.v.) were injected alone or in combination with Nf into unrestra ined, male S-D rats. At 20 +/- 2 degrees C ambient, body temperature ( Tb) was measured for 3 hr after injection. PL-017 induced dose-depende nt hyperthermia; NT, DY and U50 produced dose-related hypothermia. NT (0.0747 nmol) had no effect on PL-017-induced hyperthermia; higher dos es of PL-017/NT antagonized the hyperthermia and increased the peak an d 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 enhance d PL-017/NT-induced hypothermia but had no effect on NT-induced hypoth ermia. 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 pe ak and duration of the hypothermic response, Naloxone pretreatment (10 mg/kg s.c.) blocked the effect of U50 alone and in combination with N T, as did the peripheral opioid antagonist, naloxone methiodide (100 m g/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 i nformation on the role of NT in opioid-induced thermoregulation.