Drug Discrimination

The relative abuse liability of a novel drug is an important consideration in the development of that drug as a new medication. At Creative Biolabs, we utilize a well-established and valuable technique to assess the potential abuse liability of drug candidates, that is the drug discrimination (DD). Moreover, the paradigm can also be used to elucidate the pharmacological mechanisms and to assess the pharmacodynamic profiles of novel compounds.

Introduction of Drug Discrimination Procedure

The drug discrimination (DD) test evaluates the stimulus similarity between a test novel chemical entity and a reference agent. Rats can be trained so that when they are administered a particular drug at a specific dose, they respond on one lever for a reinforcer, such as a food pellet. When administered saline, they respond on the opposite lever for the same reinforcer.

During test sessions, the rat receives a test agent alone (generalization test) or in combination with the training drug (blockade test) to determine which lever it will press. To prevent bias, responding on either lever produces food during test sessions. Two commonly used dependent measures in a drug discrimination are the drug-appropriate responding and the rate of responding across all of the response options. The percentage of drug-appropriate responding after administration of a novel agent indicates to what degree the treatment shares discriminative stimulus effects with the training compound. Increases or decreases in the rate of responding indicate that behaviorally-active doses of a drug have been studied.

Fig.1 Schematic representation of the DD training and testing procedures. (Solinas et al. 2006)

The Features of Drug Discrimination (DD)

A number of features make DD a useful test for assessing the abuse potential of novel compounds:

• First, the effect demonstrates that the agent acts within the CNS. Compounds that fail to cross the blood-brain barrier (as determined by pharmacokinetic studies) do not function as discriminative stimuli or antagonize the discriminative stimulus (DS) effects of other agonists.
• Second, the DS properties of a compound are pharmacologically selective. That is, agents with a mechanism of action that is similar to the mechanism of the training compound will substitute for it.
• Third, the DD assay serves as a reliable model of the subjective effects of drugs that are known to play a major role in their abuse. In addition, DD studies can be used to establish duration and onset of action.

Meantime, Creative Biolabs provides other assays for the assessment of drug abuse potential:

• Conditioned Place Preference
• Intravenous Self-Administration
• Drug Dependence Liability/Withdrawal Test
• Locomotor Sensitization

An extensive range of rodent neurological disease models is placed below for your review:

Contact us if you need more information or a formal quotation.

Reference

1. Solinas, M.; et al. Using drug-discrimination techniques to study the abuse-related effects of psychoactive drugs in rats[J]. Nature Protocols. 2006, 1(3):1194-206.

For Research Use Only.