A simple animal test system to predict the likelihood of a drug causing human physical dependence.

The test system utilizes adult, male, Sprague-Dawley rats to consume their entire daily water intake in a single 60 minute session. The results of administering various doses of more than 70 therapeutic agents 15 minutes prior to the test session permit the classification of drugs into two categories. Group I drugs cause only a dose-dependent reduction in water intake, beginning at a threshold value below which no effect is seen. Group II drugs, upon reaching a threshold value, cause first a dose-dependent increase in water intake to a maximum; additional dosage increments produce a dose-dependent decrease. Group I agents include: amphetamines, antidepressants, antihistamines, antipsychotics, narcotic antagonists, parasympathomimetics, and parasympatholytics. Group II includes agents known to induce human physical dependence, namely anxiolytics, barbiturates, sedative/hypnotics, and narcotic agonists. Double-blind testing has confirmed the value of this test system as a predictive screen for identifying drugs capable of causing physical dependence.