Antisense oligodeoxynucleotide to a δ-opioid receptor messenger rna selectively blocks the antinociception induced by intracerebroventricularly administered δ-, but not μ-, ϵ-, or κ-opioid receptor agonists in the mouse

An antisense oligodeoxynucleotide to δ-opioid receptor messenger RNA was utilized to block the expression of mouse δ-opioid receptors for antinociception. The antinociception was measured by the tail-flick test in male ICR mice. Pretreatment with δ-antisense oligodeoxynucleotide (163pmol) given intracerebroventricularly twice a day for one to four days produced a time-dependent inhibition of the tail-flick response induced by intracerebroventricularly administered [D-Ala2]deltorphin II (12.8nmol). The [D-Ala2]deltorphin II-induced antinociception was significantly attenuated after three to four days of the δ-antisense oligodeoxynucleotide treatment, remained attenuated for two days and gradually recovered to the control level in four to 10 days after cessation of the pretreatment with δ-antisense oligodeoxynucleotide. Pretreatment with δ-antisense oligodeoxynucleotide (163pmol) twice a day for four days markedly attenuated the antinociception induced by intracerebroventricularly administered [D-Ala2]deltorphin II and, to a lesser extent, by D-Pen2-D-Pen5-enkephalin and morphine, but not by [D-Ala2-MePhe4-Gly(ol)5]enkephalin, β-endorphin or U50,488H. Mismatched oligodeoxynucleotide (163pmol) was ineffective against the antinociception induced by these opioids. Our results provide the evidence that the cloned δ-opioid receptor is related to the pharmacologically classified δ2-opioid receptor, and the antinociception induced by [D-Ala2]deltorphin II and, at least in part, by D-Pen2-D-Pen5-enkephalin and morphine given intracerebroventricularly is mediated by the stimulation of δ2-opioid receptors. However, δ2-opioid receptors are not involved in the antinociception induced by β-endorphin, [D-Ala2-MePhe4-Gly(ol)5]enkephalin or U50,488H given intracerebroventricularly.