Endomorphin-1 and -2 induce naloxone-precipitated withdrawal syndromes in rats.
In 1997, endomorphin-1 (EM-1) and -2 (EM-2) were identified as the most specific endogenous mu-opioid ligands. These two peptides have shown analgesic effects and many other opioid functions. In the present study, we attempt to investigate the possible ability of endomorphins to induce naloxone-precipitated withdrawal in comparison with that induced by morphine. Using the previously established scoring system in rats, 12 withdrawal signs (chewing, sniffing, grooming, wet-dog shakes, stretching, yawning, rearing, jumping, teeth grinding, ptosis, diarrhea, and penile erection) were observed and scored following naloxone (4 mg/kg, i.p.) challenge. Compared with the sham control, EM-1 and EM-2 (20 microg, i.c.v., b.i.d. for 5 days) both produced significant naloxone-induced withdrawal syndromes with similar severity to that induced by the same dose of morphine. There was no significant difference between EM-1, EM-2, and morphine-treated group for naloxone-induced withdrawal signs, except for grooming. EM-1 and EM-2 induced more grooming than that caused by morphine. Although EM-1 and EM-2 both led to the withdrawal, they displayed different potency for certain signs and suggest their distinct regulations. The present results indicate EM-1 and EM-2 could initiate certain mechanism involved opiate dependence.
Chen
J-C
JC
Department. of Pharmacology, Chang Gung University, 259 Wen Hua 1st Road, Kwei-Shan, 333, Tao-Yuan, Taiwan, ROC.
Tao
P-L
PL
Li
J-Y
JY
Wong
C-H
CH
Huang
E Y-K
EY
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D007274:Injections, Intraperitoneal; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome / Q000209:etiology*
D000701:Analgesics, Opioid; D009842:Oligopeptides; C105293:endomorphin 1; D009270:Naloxone; C105294:endomorphin 2; D009020:Morphine