Abstract

Drugs which cause physiological dependence, addiction or behavioral dependence have different primary molecular mechanisms of action. However, they all can enhance dopaminergic neurotransmission on the midbrain-forebrain axis, and after repeated use of such drugs complex alterations in gene expression and neuronal morphology occur in the ventral tegmental area, nucleus accumbens, and many adjacent brain regions. Drug dependence has an obvious heritability component, but interaction of genetic predisposition with environmental factors, most importantly the availability of the drug, plays a pivotal role. Stress enhances drug use and on this basis the development of addiction; stress also precipitates relapses. These effects of stress appear to be
mediated by the release of corticotropin-releasing factor and subsequent downstream changes, some of which are likely to occur in dopaminergic neurotransmission. Pre-existent variability and elicited shifts in such domains as impulse control, decision making and memory, and in the corresponding neural circuits, contribute importantly
to the development of addiction. Understanding and acknowledging the biological nature of substance dependence will importantly contribute to the attitudes towards their treatment, and towards revision of public health policies.