E Tagashire | PubMed Health

PubMed1975

[Dependence on and preference for morphine (II). Comparison among morphine, phenobarbital and diazepam].

Results of a previous experiment indicated that naive rats given a choice between morphine-admixed food (0.5 similar to 1mg/g of food) and quinine-admixed food (0.5 similar to 1 mg/g of food) for 3 weeks gradually and spontaneously preferred the morphine-admixed food, and this choice behavior revealed one of the psychological aspects of morphine dependent rats. In the present work, the ability of preference formation was detected for morphine, phenobarbital and diazepam by a defferent chioce test using drug dependent rats. Rats were pretreated with morpnine, phenobarbital, and/or diazepam by drug admixed food ingestion method for 12 similar to 15 weeks, and the choice test was practiced for one week at 3 intervals (4 similar to 5 trials). Control groups of rats were given the same choice testas the naive rats. Results indicated that (a) of all the drugs employed, morphine showed the most rapid and intensive preference formation (b) Phenobarbital and diazepam had almost the same degree of preference formation. (c) Phenobarbital showed no dose-dependent intensity of preference formation in the 50-90 mg/kg/day dose range, however, a more rapid development of preference was observed dose-dependently among the 80-120 mg/kg/day dose range of diazepam. Thus these studies utilizing a choice test provide a clear demonstration of drug-seeking behavior in rats. In addition, the present method is useful for drug screening tests involving weak psychological dependence liability, and moreover, the data could be analyzed statistically.

Animals↗

PubMed1975

[A study on drug dependence using fast acting drugs].

Physical dependence on narcotics is induced in laboratory animals by intermittent parenteral administration (2 approximately 3 times daily). However, inducing of dependence on pethidine has been unsuccessful using the parenteral method. Recently, it has been reported that physical dependence on pethidine can be induced by continuous infusion methods (5.6). In the present experiment, pethidine was administered to rats (n=5 approximately 6) by ingestion of pethidine-admixed food preparations (0.5 approximately 4.0 mg/g of feed). The results indicated that (a) when rats are allowed free access to two food preparations (0.5 mg/g vs. 1 mg/g of food) for 7 weeks, spontaneous intake ratios of food (1 mg/g of food) gradually increased from 15% to 30% after 3 weeks. (b) Abrupt withdrawal for 48 hr after a 10 day administration period (2 mg/g of food on day 1 approximately 3 and 4 mg/g of food on day 4 approximately 10) resulted in a loss of body weight in the next 24 hr, and the prewithdrawal level of body weight was recovered in 48 hr. (c) The time course of body weight and food intake during the first 24 hr withdrawal period demonstrated the characteristic pattern of abstinence syndrome of pethidine, viz. early onset (12 approximately 13 hr) and rapid recovery (within 48 hr), as compared to morphine withdrawal. (d) Suppression of pethidine abstinence of both a single injection of morphine (10 mg/kg, s.c.) and substitution for morphine-admixed food was also realized. (e) When levallorphan (5 mg/kg, s.c.) was administered to both pethidine and morphine dependence rats, the maximal decrease in body weight was less than that in morphine dependent rats. These data indicate that pethidine possesses about one fifth the dependence liability of morphine and the maximal abstinence syndrome appears within 24 hr after withdrawal. Conclusively, application of a drug-admixed food preparation in drug dependence tests in rats has proven to be a useful method, particularly in the case of pethidine-like drugs which rapidly disappear from the blood.

Animals↗