Evidence in vivo has suggested the existence of subtypes of the δ opioid receptor (DOR), which have been termed δ1 and δ2. These proposed DOR subtypes are thought to be activated by [D-Pen2, D- Pen5]enkephalin (DPDPE, δ1) and [D-Ala2, Glu4]deltorphin (δ2). Recent work in which an antisense oligodeoxynucleotide (oligo) to a cloned DOR was administered by the intrathecal (i.th.) route has demonstrated a reduction in the antinociceptive actions of both i.th. DPDPE and [D-Ala2, Glu4]deltorphin, but not of [D-Ala2, NMPhe4, Gly-ol]enkephalin (DAMGO, μ agonist) in mice. The present investigation has extended these observations by administering the same DOR antisense oligo sequence by the intracerebroventricular (i.c.v.) route and evaluating the antinociceptive actions of i.c.v. agonist selective for δ, μ and κ receptors. I.th. treatment with DOR antisense oligo, but not mismatch oligo, significantly inhibited the antinociceptive actions of both i.th. DPDPE and [D-Ala2, Glu4deltorphin but not of i.th. DAMGO or U69, 593 (κ agonist), confirming previous data. In contrast, i.c.v. DOR antisense oligo, but not mismatch oligo, seletively inhibited the anitinociceptive response to i.c.v. [D-Ala2, Glu4]deltorphin without altering the antinociceptive actions of i.c.v. DPDPE, DAMGO or U69,593. The data suggest that the cloned DOR corresponds to that pharmacologically classified as δ2 and further, suggest that this δ receptor subtype may play a major role in eliciting spinal δ-mediated antinociception.
- Glu]deltorphin antinociception
- antisense oligodeoxynucleotides
- opioid δ receptor subtypes
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Pharmacology, Toxicology and Pharmaceutics(all)