Assessment of morphine-type physical dependence liability: a screening method using the rat.
The effects of centrally acting drugs on body weight changes during 8-h periods in the daytime were studied in the rat in attempts to relate those effects with morphine-type physical liability. Repeated administration of drugs which have morphine-type physical dependence liability altered the prevailing pattern of continuous body weight decrease during the observation period in control animals to an initial increase and subsequent decrease. Withdrawal of these drugs following chronic drug treatment caused a precipitous loss of body weight. Such a body weight loss was further enhanced by the administration of naloxone. In chronically morphine-treated animals, substitution for morphine with a single dose of a test drug caused an increase in body weight or attenuated the loss of body weight due to morphine withdrawal when the test drug has physical dependence liability. Drugs may be classified according to their effects on body weight changes into several groups, each with different physical dependence liability. It is concluded that physical dependence liability of centrally acting drugs can be predicted simply, inexpensively and objectively, by their effects on the pattern of daily body weight changes.
D000818:Animals; D001835:Body Weight / Q000187:drug effects*; D002940:Circadian Rhythm / Q000187:drug effects; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006801:Humans; D008297:Male; D009021:Morphine Dependence; D009270:Naloxone / Q000494:pharmacology; D051381:Rats; D019966:Substance-Related Disorders
D009270:Naloxone