Although the interactions between the mu- and the delta-
opiate receptor subtypes are well documented with regard to supraspinal
analgesia, less is known about the mutual interactions on
respiratory depression. To clarify the functional interactions between both
opiate receptor subtypes with regard to antinociception and
respiratory depression, male Wistar rats were intravenously injected with 2.5 microg/kg of the mu-
opiate agonist
sufentanil and subsequently intravenously challenged with the delta antagonist
naltrindole (NTI) or
naltrindole 5'-isothiocyanate (5'-NTII), a delta-2 antagonist. Antinociception was measured by means of the tail-flick latency, and
respiratory depression was evaluated by means of analysis of PaCO2, PaO2, and oxygen saturation. To quantify the antagonistic properties of NTI and 5'-NTII, mean areas under the curve were calculated for groups treated with
sufentanil, control vehicle, and
sufentanil plus a dose of the antagonists. NTI, but not 5'-NTII, antagonized the
sufentanil-induced antinociception
at 10 mg/kg NTI. Below this dose the effects were inconsistent. The
sufentanil-induced
hypercapnia and
hypoxia were diminished with 10 mg/kg NTI or 5'-NTII. These data indicate that NTI antagonizes the
sufentanil-induced antinociception and
respiratory depression in rats. A dissociation between the antinociception and
respiratory depression following intravenous
sufentanil could be obtained with 10 mg/kg 5'-NTII pointing to different regulatory effects of
opiate delta receptor subtypes on mu-
opiate agonist-induced behavioral effects.