Non-Precipitated Withdrawal Test

More elaborate procedures can be employed to assess whether drug withdrawal induces changes in fearfulness, pain sensitivity, convulsive threshold or even memory. On the other hand, it is frequently difficult to demonstrate effects on these parameters and the tests involved are particularly time-consuming. The procedure described below represents an initial screen which has been shown to be sensitive to several dependence-inducing drugs such as opioids and benzodiazepines (Goudie et al. 1993). 

Whereas many CNS safety tests evaluate multiple doses, we recommend the inclusion of just two doses for non-precipitated withdrawal studies. The low dose should be close to the dose inducing clear effects in the test predictive of the substance s therapeutic indication. The high dose should be the maximally tolerated dose as determined, for example, from an Irwin test. If it can be shown that the test substance can be repeatedly administered at a maximally tolerated dose under conditions where similar treatment with an appropriately chosen reference substance induces 

Twelve animals are studied per group. The test is performed blind. 

The experiment includes a control group pretreated with the vehicle twice daily for 20 days. 

Differences from control are evaluated on a day-by-day basis using non-paired Student s t-tests. 

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