Physical dependence of a dermorphin tetrapeptide analog, [D-Arg2, Sar4]-dermorphin (1-4) in the rat.
The characteristics of an analog of tetrapeptide dermorphin (H-Tyr-D-Arg-Phe-Sar-OH), [D-Arg2, Sar4]-dermorphin (1-4) were examined in comparison with morphine by the appearance of typical withdrawal signs upon cessation of administration or treatment with naloxone, an opioid antagonist. The dose of [D-Arg2, Sar4]-dermorphin (1-4) or morphine in the physical dependence test can be quantified by determining the ED50 to inhibit the tail-flick response to thermal stimuli. Doses from 8 to 64 times the ED50 doses were employed in the subcutaneous injection schedules. The cessation of [D-Arg2, Sar4]-dermorphin (1-4) or naloxone treatment was largely without effect on body weight, in contrast to a marked loss of weight in morphine-dependent rats. The tetrapeptide failed to substitute for morphine in morphine-dependent rats. The physical dependence of [D-Arg2, Sar4]-dermorphin (1-4) was revealed by the behavioral signs of withdrawal precipitated by naloxone. However, the scores of lacrimation, diarrhea and urination were much lower in chronically tetrapeptide-treated rats than in morphine-treated rats, though the score of teeth chatter was higher. These findings indicate that [D-Arg2, Sar4]-dermorphin (1-4) may differ from morphine in physical dependence.
D000700:Analgesics; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011930:Reaction Time / Q000187:drug effects; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology; D019966:Substance-Related Disorders / Q000503:physiopathology*; D013997:Time Factors
D000700:Analgesics; D009294:Narcotics; D009842:Oligopeptides; C047133:dermorphin (1-4), Arg(2)-Sar(4)-; D009270:Naloxone; D009020:Morphine