[Neurobiological principles of drug dependence. Exemplified by opioids and psychostimulants]

Abstract

New insights into the neurobiological mechanisms underlying drug addition have become available with recent advances in experimental research. This is particularly true for the opioids and psychostimulants: behavioural and biochemical studies have revealed that activation of the mesolimbic "reward pathways", involving the release of dopamine, which acts upon D1 receptors, plays a critical part in the development of addictive behaviour. In the case of the opioids, the differentiation of various types of receptors (and of the corresponding endogenous ligands, the endorphins) revealed a bidirectional role of opioid receptors in this process: stimulation of the reward system, mediated by mu- and delta-opioid receptors, and inhibition of the reward pathways, mediated by the activation of chi-receptors. Thus, a functional equilibrium between these tonically active opioidergic systems appears to provide a neutral motivational state. During drug withdrawal, the decrease in dopamine release most probably reflects a disturbance of this equilibrium. There is increasing evidence that endogenous opioidergic mechanisms also modulate addictive behaviour caused by psychostimulants and other drugs of abuse. This article discusses the implications of these new findings in the context of pharmacotherapeutic strategies in the treatment of addictive behaviours.