Studies On The Interaction Of Opioid And NPFF Systems In Thermoregulation

Opioid receptors are currently classified as classical (MOP, DOP and KOP receptors) and nonclassical (NOP receptor). Opioid receptors are involved in the physiological control of numerous functions of the central nervous system, including thermoregulation. For example, morphine could produce a range of effects on body temperature in a number of species including man, which acted on the classical opioid receptors with lower doses producing hyperthermia and higher doses resulting in hypothermia. NOP receptor is the fourth member of the opioid receptor family. And N/OFQ could activate NOP receptor and decrease body temperature in rats. In addition, the previous studies indicated that NPFF might act as a modulator of endogenous opioid functions. NPFF injected into the third ventricle could elicit a marked decrease in basal rectal temperature in mice. It was worthy to note that NO participates in hypothermia evoked by both NPFF and morphine.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 (30 nmol) 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 (5 nmol,) or nociceptin/orphanin FQ (N/OFQ) (2 nmol). Neither the classical opioid receptors antagonist naloxone (10 nmol) nor NOP receptor antagonist [Nphe1]NC(1-13)NH2 (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.