The Effects of Intravenous Naltrindole and Naltrindole 5′-Isothiocyanate on Sufentanil-Induced Respiratory Depression and Antinociception in Rats

Abstract

Although the interactions between the μ- and the δ-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 μg/kg of the μ-opiate agonist sufentanil and subsequently intravenously challenged with the delta antagonist naltrindole (NTI) or naltrindole 5′-isothiocyanate (5′-NTII), a δ-2 antagonist. Antinociception was measured by means of the tail-flick latency, and respiratory depression was evaluated by means of analysis of PaCO 2, PaO 2, 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 δ receptor subtypes on μ-opiate agonist-induced behavioral effects.