Functional neurotoxicity of drugs of abuse

The epidemic growth of the use of controlled substances has brought their toxic effects to clinical attention. Several drugs of abuse are known to induce nerve cell toxicity after acute and chronic administration. In addition, it has been suggested that the three main classes of abused substances, namely psychostimulants, ethanol and opiates, also induce changes in the function of discrete neural pathways. These alterations may eventually be responsible for the loss of behavioral control often observed during the natural history of the addiction process. Therefore, biochemical and behavioral toxicity deserve equal attention. A complex neural network within the forebrain limbic system which has been characterized over the past few years seems to mediate drug-seeking behavior and maintain drug self-administration in rodents. A striking similarity has been observed between this circuit and the neural substrates of motivated behavior. This review focuses on the possibility that drugs of abuse may acquire significance as reinforcers by usurping the physiological role of this circuit which normally operates to ensure survival of the individual. This may represent a subtle mechanism through which drugs of abuse may induce behavioral toxicity even in the absence of nerve cell loss.