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.
Handler
C M
CM
Department of Pharmacology, Temple University School of Medicine, Philadelphia, Pennsylvania, USA.
Mondgock
D J
DJ
Zhao
S F
SF
Geller
E B
EB
Adler
M W
MW
D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects*; D004723:Endorphins / Q000494:pharmacology; D008297:Male; D009270:Naloxone / Q000031:analogs & derivatives / Q000494:pharmacology; D009496:Neurotensin / Q000494:pharmacology*; D000644:Quaternary Ammonium Compounds; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000819:agonists*
D004723:Endorphins; D000644:Quaternary Ammonium Compounds; D011957:Receptors, Opioid; D009270:Naloxone; D009496:Neurotensin; C041269:N-methylnaloxone; C044708:morphiceptin, N-Me-Phe(3)-