Abstract: |
Antisense oligodeoxynucleotides directed against various G protein α subunits differentially block the analgesic actions of μ-, δ- and κ- opioid agonists in mice. Intracerebroventricular administration of oligodeoxynucleotides targeting G(iα2), G(oα), and G(sα) block supraspinal μ-opioid analgesia, whereas G(iα2) and G(x/zα) antisense probes block spinal μ analgesia. Although supraspinal and spinal morphine- 6β-glucuronide (M6G) analgesia also is sensitive to these antisense treatments, its sensitivity profile differs from that of morphine, implying the existence of a different analgesic system. G(iα1) and Gx/zα antisense probes block supraspinal M6G analgesia, whereas G(iα1), G(iα3), G(oα), and G(x/zα) antisense probes block spinal M6G analgesia. Spinal δ-opioid analgesia is blocked by antisense probes to all of the G protein α subunits tested, whereas κ1-opioid analgesia is sensitive to only G(qα). The κ3 agonist naloxone benzoylhydrazone produces its analgesia through supraspinal mechanisms and is blocked by G(iα1), G(iα3), G(sα), G(qα), and G(x/zα) antisense oligodeoxynucleotides. Together, these results support the presence of seven different analgesic systems for these various opioid agonists. |