Neuropeptide FF receptors antagonist, RF9, attenuates opioid-evoked hypothermia in mice.
The present study used the endpoint of hypothermia to investigate opioid and neuropeptide FF (NPFF) interactions in conscious animals. Both opioid and NPFF systems played important roles in thermoregulation, which suggested a link between opioid receptors and NPFF receptors in the production of hypothermia. Therefore, we designed a study to investigate the relationship between opioid and NPFF in control of thermoregulation in mice. The selective NPFF receptors antagonist RF9 (30nmol) injected into the third ventricle failed to induce significant effect, but it completely antagonized the hypothermia of NPFF (45 nmol) after cerebral administration in mice. In addition, RF9 (30 nmol) co-injected i.c.v. in the third ventricle reduced the hypothermia induced by morphine (5nmol,) or nociceptin/orphanin FQ (N/OFQ) (2 nmol). Neither the classical opioid receptors antagonist naloxone (10 nmol) nor NOP receptor antagonist [Nphe(1)]NC(1-13)NH(2) (7.5 nmol) reduced the hypothermia induced by the central injection of NPFF at dose of 45 nmol. Co-injected with a low dose of NPFF (5 nmol), the hypothermia of morphine (5 nmol) or N/OFQ (2 nmol) was not modified. These results suggest that NPFF receptors activation is required for opioid to produce hypothermia. In contrast, NPFF-induced hypothermia is mainly mediated by its own receptors, independent of opioid receptors in the mouse brain. This interaction, quantitated in the present study, is the first evidence that NPFF receptors mediate opioid-induced hypothermia in conscious animals.
Wang
Yi-Qing
YQ
Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Lanzhou University, 222 Tian Shui South Road, Lanzhou 730000, PR China.
Guo
Jia
J
Wang
Sheng-Bin
SB
Fang
Quan
Q
He
Feng
F
Wang
Rui
R
D000218:Adamantane / Q000031:analogs & derivatives* / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D019540:Area Under Curve; D001833:Body Temperature Regulation / Q000187:drug effects*; D004151:Dipeptides / Q000494:pharmacology*; D004347:Drug Interactions; D007035:Hypothermia / Q000139:chemically induced / Q000378:metabolism; D007700:Kinetics; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D018847:Opioid Peptides / Q000494:pharmacology; D018013:Receptors, Neuropeptide / Q000037:antagonists & inhibitors*; D000097629:Nociceptin
D000218:Adamantane; D000701:Analgesics, Opioid; D004151:Dipeptides; D009020:Morphine; D009270:Naloxone; D018847:Opioid Peptides; D018013:Receptors, Neuropeptide; D000097629:Nociceptin; C508361:adamantylcarbonyl-arginyl-phenylalaninamide; C083929:neuropeptide FF receptor