Induction of physical dependence on morphine in mice by the drug-admixed food method.
The drug-admixed food method was applied to ICR strain mice for studying development of physical dependence on morphine. Mice were treated with morphine-admixed food of increasing concentration (1, 2 and 3 mg/g food) every third day for 9 days. During the treatment, the mice did not show any signs of toxicity. Plasma and brain morphine levels were quantitatively related to the morphine concentration in drug-admixed food. The plasma morphine level showed a circadian rhythm, and the level was higher than 0.15 microgram/ml throughout the day. The morphine-treated mice manifested body weight loss, diarrhea and ptosis from 4 hr after morphine withdrawal and showed maximum body weight loss at 12 hr. In the naloxone-precipitated test, jumping and body shakes were observed in mice treated with morphine-admixed food (2 mg/g food) at least for 1 day. Moreover, in mice treated with morphine (2 mg/g food) for 3 days, marked jumping and body shakes and some writhing were observed after naloxone administration. These results suggest that the drug-admixed food method has advantages of easily and rapidly inducing the physical dependence on morphine in mice without causing toxicity and death.
D000821:Animal Feed; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D005247:Feeding Behavior / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000008:administration & dosage / Q000378:metabolism; D009021:Morphine Dependence / Q000503:physiopathology*; D009270:Naloxone / Q000494:pharmacology; D013375:Substance Withdrawal Syndrome / Q000139:chemically induced; D013997:Time Factors
D009270:Naloxone; D009020:Morphine