Comparison of drug toxicity: neurobiological mechanisms of drug addiction and therapeutic approaches

In humans as in animals, individual differences in the response to drug of abuse and in the proneness to self-administer these compounds have been obs erved. Many factors, such as genetics, history of drug use, stress and life events likely contribute to drug-addiction. Gene deletion was largely use in association with inhibitors of neuropeptide inactivating enzyme to Inves tigate the neurochemical basis of drug addiction. The mesolimbic dopamine s ystem has been clearly demonstrated to be critically involved in rewarding effects of all drugs of abuse. Addiction could be a dopamine-dependent asso ciative learning disorder. In contrast to natural rewards, drugs of abuse h ave nonhabituating effects leading to sensitization of the DA systems and o verestimation of the expected drug-induced sensation of pleasure. Numerous results emphasize the important role of endogenous opioids in the mechanism of drug addiction which could be related to the imbalance between stimulat ion of mu vs delta receptors and/or defects in the equilibrium between rewa rding (opioid) and counteracting (CCK, SP...) systems. The identity in the mechanism subtaining the abuse of illicits as well as licits (ex. alcohol) drugs has been taken into account to extend the role of the French organiza tion against drug abuse.