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.