Is the nociceptin (NOP) receptor involved in attenuation of the expression of sensitization to morphine-induced hyperlocomotion in mice?
In the present study we investigated whether synthetic agonists of the nociceptin (NOP) receptors, Ro 64-6198 [(1S,3aS)-8-(2,3,3a,4,5,6-hexahydro-1H-phenalen-1-yl)-1-phenyl-1,3,8-triaza-spiro[4,5]decan-4-one] and Ro 65-6570 (8-acenaphthen-1-yl-1-phenyl-1,3,8-triaza-spiro[4.5]decan-4-one), influence the expression of sensitization to the locomotor stimulant effect of morphine in mice. Sensitization was produced by five repeated administrations of morphine (10 mg/kg, s.c.) at 3-day intervals. Seven days after the last morphine injection, Ro 64-6198 (1 and 3 mg/kg, i.p.) and Ro 65-6570 (3 and 6 mg/kg, i.p.) were given immediately before the challenge dose of morphine (10 mg/kg, s.c.). Both substances inhibited the expression of sensitization to the locomotor stimulant action of morphine. However, the selective NOP receptor antagonist, [Nphe1]NC(1-13)NH2 (30 nmol, i.c.v.) did not reverse the inhibitory effect of the Ro-compounds. Therefore, our results suggest that the NOP receptor may not be critical for the influence of Ro-compounds on the morphine-induced sensitization, or the observed effect may be attributed to one functional subset of this receptor, stimulation of which is not blocked by [Nphe1]NC(1-13)NH2.
Kotlinska
J
J
Department of Pharmacodynamics, Medical University of Lublin, Lublin, Poland. jolka@panaceum.am.lublin.pl
Rafalski
P
P
Talarek
S
S
Dylag
T
T
Rolka
K
K
Wichmann
J
J
Silberring
J
J
D000818:Animals; D004351:Drug Resistance; D007093:Imidazoles / Q000494:pharmacology*; D008124:Locomotion / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D009619:Nociceptors / Q000187:drug effects* / Q000502:physiology*; D013141:Spiro Compounds / Q000494:pharmacology*
C121726:8-acenaphthen-1-yl-1-phenyl-1,3,8-triazaspiro(4.5)decan-4-one; D007093:Imidazoles; D009294:Narcotics; C408068:Ro 64-6198; D013141:Spiro Compounds; D009020:Morphine