[Comparison of three methods of inducing physical dependence to morphine in rats using short-term medication]

A comparison of several methods for developing physical dependence to morphine was made. Male Sprague-Dawley rats were treated with morphine-admixed food (drug-admixed food, DAF; 0.5 and 1 mg/g food), morphine slow release emulsion (SRE; 75, 100 and 150 mg/kg) and morphine (75 mg) pellets. In the SRE and pellet methods, the typical signs of morphine toxicity, such as catatonia, exophthalmos and shallow respiratory movements, were observed 15-20 min after the treatment and these signs were maintained for 14-18 hr. In rats treated with SRE and pellets, plasma morphine levels reached a maximum 1 day after the morphine treatment, and subsequently decreased, while plasma morphine levels in rats treated with DAF increased treatment period-dependently. Withdrawal signs precipitated by naloxone (3 mg/kg, sc) in rats treated with DAF, SRE and pellets were characterized by loss of body weight, shaking, vocalization, diarrhea, ptosis, tooth-chattering, nose bleed, salivation and lacrimation. Naloxone-precipitated withdrawal signs reached a maximum 1-2 days after treatment with SRE and pellets, and were correlated with the duration of DAF treatment. Rats treated with DAF, SRE (150 and 225 mg/kg) and pellets for 3 days, manifested loss of body weight, diarrhea etc. after the morphine withdrawal. Maximum body weight loss in each group was 7-10% at 1-2 days after the morphine withdrawal. It was thus, concluded that physical dependence on morphine can be induced rapidly by these three methods. However, the SRE and pellet methods induced morphine toxicity and it was difficult to maintain physical dependence on morphine in these rats.(ABSTRACT TRUNCATED AT 250 WORDS)