Nociceptin/orphanin FQ (N/OFQ) induces a quasi-morphine abstinence syndrome in the rat.
Nociceptin/orphanin FQ (N/OFQ) is a neuropeptide that exerts antiopiate effects under some circumstances, and there is evidence that it contributes to opiate tolerance. This raises the question, might N/OFQ also contribute to opiate dependence and abstinence? Twenty-two male Sprague-Dawley rats were cannulated in the third ventricle and challenged 7 days later by third ventricle injection of 50, 200 or 1,000 ng N/OFQ or saline alone. Each rat was observed under "blind" conditions for 30 min beginning 15 min after onset of the third ventricle injection. There was a significant positive linear trend of signs as a function of N/OFQ dose. Subjects receiving saline had 18.0+/-2.0 (mean+/-SEM) overall abstinence-like signs, whereas subjects receiving 50, 200 or 1000 ng N/OFQ had 35.2+/-3.6, 49.8+/-2.6 and 63.5+/-9.7 signs, respectively. In 16 additional rats, abstinence-like signs induced by 1000 ng N/OFQ were significantly attenuated by low SC doses of morphine or clonidine. These results raise the possibility that N/OFQ might contribute to opiate dependence and subsequent abstinence syndrome. On the other hand, N/OFQ over a wide dose range induced abstinence signs with similar potency in morphine dependent and non-dependent rats.
Malin
D H
DH
University of Houston-Clear Lake, TX 77058, USA. Malin@cl.uh.edu
Lake
J R
JR
Moon
W D
WD
Moy
D
D
Montellano
A L
AL
Moy
E
E
Campbell
T D
TD
Bell
M V
MV
Bryant
D
D
Harrison
L M
LM
Grandy
D K
DK
D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D009020:Morphine / Q000009:adverse effects*; D009021:Morphine Dependence / Q000188:drug therapy; D018847:Opioid Peptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome / Q000209:etiology*; D000097629:Nociceptin
D003000:Clonidine; D009020:Morphine; D018847:Opioid Peptides; D000097629:Nociceptin