Antisense oligodeoxynucleotide to a δ-opioid receptor blocks the antinociception induced by cold water swimming

Abstract

The type of opioid receptors in the spinal cord involved in antinociception induced by cold water swimming (CWS) was studied in male ICR mice. Mice were submitted to CWS for 3 min and antinociception was measured 7 min after the CWS by the tail-flick test. Intrathecal (i.t.) injection of naltrindole (NTI, 5 μg) which blocked i.t. DPDPE ([ d-Pen 2, d-Pen 5]enkephalin, 5 μg)-induced antinociception, blocked the CWS-induced antinociception. On the other hand, i.t. injection of CTOP ( d-Phe-Cys-Try- d-Try-Orn-Thr-Pen-Thr-NH 2, 50 ng) and norbinaltorphimine (nor-BNI, 5 μg) which blocked i.t. DMAGO ([ d-Ala 2,NHPhe 4,Gly-ol]enkephalin, 10 ng)- and U50,488H ( trans(±)-3,4-dichloro- N-methyl- N-[2-(1-pyrrolidinyl)-cyclohexyl]benzeneacetamide, 75 μg)-induced antinociception, respectively, did not block CWS-induced antinociception. Intrathecal pretreatment with antisense oligodeoxynucleotide to δ-opioid receptor mRNA (δ-AS oligo, 163 pmol) once a day for 1 to 3 days caused a time-dependent attenuation of CWS-induced antinociception. δ-AS at doses from 1.6 to 163 pmol pretreated i.t. for 3 days caused a dose-dependent blockade of CWS-induced antinociception. However, i.t. pretreatment with mismatch oligodeoxynucleotide (MM oligo, 163 pmol) for 3 days did not affect the CWS-induced antinociception. The results indicate that CWS-induced antinociception is mediated by the stimulation of δ-opioid receptors in the spinal cord.