Enkephalin analogs and physical dependence.
A novel method of drug delivery, the osmotic minipump, was used to measure the ability of morphine and eight enkephalin analogs to produce physical dependence. After 3 days of morphine or peptide infusions into the rat brain, the dependent state was established and revealed by naloxone challenge; escape behavior, shaking, tachycardia and an increased respiration rate provided objective evidence of withdrawal. The minipump method required only small amounts of test materials; 6 micrograms of morphine sulfate or 0.17 microgram of FK 33,824, the most potent enkephalin analog, infused for 3 days per rat, were sufficient to induce dependence in all animals tested at these dose levels. A positive rank correlation was obtained between the short-term activities of the eight enkephalin analogs in inhibiting a motor response to a noxious stimuli and the long-term activities of the enkephalin analogs in producing physical dependence.
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D004343:Drug Implants; D004723:Endorphins / Q000494:pharmacology*; D004745:Enkephalins / Q000008:administration & dosage / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology; D051381:Rats; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology; D019966:Substance-Related Disorders / Q000209:etiology* / Q000503:physiopathology
D004343:Drug Implants; D004723:Endorphins; D004745:Enkephalins; D009294:Narcotics; D009270:Naloxone