Effects of an antisense oligonucleotide to pronociceptin and long-term prevention of morphine actions by nociceptin.
To further characterize the anti-opioid action of the neuropeptide nociceptin, we examined the effects of the repeated intracerebroventricular (i.c.v.) treatment (once daily for 4 days) with an antisense oligodeoxynucleotide complementary to pronociceptin mRNA, in the rat. We also investigated possible changes of the antinociceptive and hyperthermic effects induced by the i.c.v. administration of morphine, in rats i.c.v. pretreated with nociceptin 3 h before. The pretreatment with the antisense oligodeoxynucleotide, but not with a mismatched sequence (used as a control), caused an increase in spontaneous locomotor activity and produced a potentiation of the antinociceptive effect of a submaximal dose of i.c.v. morphine (1 microgram/rat). The i.c.v. pretreatment with nociceptin (2 nmol/rat, 3 h before) prevented both the antinociceptive and the hyperthermic effects of morphine (10 microgram/rat i.c.v.). These results strengthen the hypothesis of an anti-opioid action of nociceptin at supraspinal level and suggest that the neuropeptide may exert long-term modulatory effects.
Candeletti
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Department of Pharmacology, University of Bologna, Irnerio 48, 40126, Bologna, Italy. candelet@biocfarm.unibo.it
Ferri
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D000701:Analgesics, Opioid / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000187:drug effects; D008297:Male; D009020:Morphine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage / Q000494:pharmacology*; D018847:Opioid Peptides / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology; D011498:Protein Precursors / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000235:genetics* / Q000378:metabolism; D013997:Time Factors; D014665:Vasodilator Agents / Q000494:pharmacology; D000097629:Nociceptin
D000701:Analgesics, Opioid; D009020:Morphine; D016376:Oligonucleotides, Antisense; D018847:Opioid Peptides; D011498:Protein Precursors; D012333:RNA, Messenger; D011957:Receptors, Opioid; D014665:Vasodilator Agents; D000097629:Nociceptin; C119224:pronociceptin