Role of pharmacokinetic and pharmacodynamic parameters in neuroadaptations induced by drugs of abuse, with a focus on opioids and psychostimulants.

The purpose of this review is to illustrate the importance of pharmacodynamic and pharmacokinetic factors in the complexity of the behavioral and neurochemical adaptations that occur following chronic treatments with drugs of abuse, with a focus on opioids and psychostimulants. As these neuroadaptations are thought to contribute to the pathogenesis and persistence of addiction, it is important to well understand how they can be modulated. The experimental results clearly show that changes observed are depending on the binding properties of the ligands, drug administration patterns, brain structures considered, and withdrawal periods. Thus, pharmacodynamic and pharmacokinetic factors play a key role, and may highly contribute to the great heterogeneity of the results reported in the literature regarding neuroadaptations observed following repeated treatments with drugs of abuse, each investigator using different protocols and/or different ligands, even if their targets/receptors are the same.