Congrès annuel SFT - Paris, 23-24 octobre 2006
"Toxicologie de la pharmacodépendance aux médicaments et aux drogues" Stratégies d'évaluation Roger D. PORSOLT Drug abuse is conceptually different from drug dependence although both can co-exist with the same substance class. Abuse refers to the non-medical or over-use of a given substance with subsequent disruption of normal function. Substance characteristics which predict a liability for abuse are: central action, rapid onset, high solubility, tolerance, similarity to other drugs of abuse and, most importantly, positive reinforcing properties. Substance classes associated with abuse are opioids, sedative hypnotics/tranquillizers, psychostimulants, hallucinogens, cannabinoids, nicotine-like drugs and chemical precursors of these agents. Tests for tolerance administer the test substance repeatedly over several days and then demonstrate a waning of the major effect as a result of this repeated treatment. Existence of tolerance increases the probability that the test substance will be abused. Tests for similarity can simply examine the behavioral profiles of the test substance in comparison with known substances of abuse. A much more powerful method is the drug discrimination procedure. When under the influence of a given drug of abuse, pressing on one lever in a Skinner Box (left or right) will yield a food reward whereas pressing on the other lever is without consequence. Conversely, when under the influence of vehicle, pressing on the other lever will yield a reward. Animals can thereby learn to recognize the presence of the training drug and to indicate whether the test substance resembles it. A first estimate of the reinforcing properties of a test substance is the conditioned place preference procedure. Animals are given repeated sessions during which the test substance is always associated with a given environment, usually one compartment of a two compartment box, and vehicle with the other compartment. On the test day, without drug, the animals are given a free choice between the two compartments. Preference for the compartment previously associated with the test substance is an indication that the substance possesses positive reinforcing properties. The most direct test for positive reinforcing properties is whether an animal, previously implanted with indwelling catheters, will press a lever to obtain an i.v. infusion of the test substance. The advantages and disadvantages of each procedure will be critically discussed. |
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