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 nocicept in, 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 possi ble changes of the antinociceptive and hyperthermic effects induced by the i.c.v. administration of morphine, in rats i.c.v. pretreated with nocicepti n 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 antinocic eptive effect of a submaximal dose of i.c.v. morphine (1 mu g/rat). The i.c .v. pretreatment with nociceptin (2 nmol/rat, 3 h before) prevented both th e antinociceptive and the hyperthermic effects of morphine (10 mu g/rat i.c .v.). These results strengthen the hypothesis of an anti-opioid action of n ociceptin at supraspinal level and suggest that the neuropeptide may exert long-term modulatory effects. (C) 2000 Elsevier Science Inc. All rights res erved.