All of them act by attachment to specifc receptors in the central nervous system that mobilise neurotransmitters activating or inhibiting neuronal activity in various complex biochemical and electrophysiological patterns at synaptic junctions. With repetitive use of psychoactive substances, receptor up‑regulation and an increase in enzyme induction (required for degradation of the drug) form the biochemical basis of tolerance. Neuroscience and modern imaging techniques that visualise brain activity have shown that three brain areas play a predominant role in the response to psychoactive drugs and the development of dependency: the ventral teg‑ mental area, the mesolimbic dopamine system and the cortex. All psychoactive substances provoke a rewarding sensation in the same manner and in the same brain areas as the stimuli that are critical to survival, such as feeding and reproduction. Dopamine increase in the mesolimbic dopamine system, the biochemical reaction to all unexpected rewards, has been meas‑ ured as much higher under psychoactive drugs than under natural stimuli such as food intake. The mesolimbic dopamine system also plays a major role in emotional motivation and reinforcement learning processes, a mechanism that, in combination with neuronal reorganisation – “synaptic plasticity” – for cortical (sensory) and limbic (emotional) projection, may represent the bio‑ behavioural background of dependency.5 5.2 Drug dependency and addiction Despite such biological reactions increasingly identifed by neuroscience research, not everybody who consumes psychoactive drugs becomes depend‑ ent on or addicted to psychoactive substances. The term “addiction” relates generally to compulsive behaviour, not only substance‑related but also, for example, gambling. Dependency There are a number of factors, apart from the chemical structure of a substance and its biological reactions in the brain, that foster the development of drug dependency or drug addiction: X the substance, its availability, dose, frequency, duration of consumption and route of application, can play a role; 5. WHO: Neuroscience of psychoactive substance use and dependence (Geneva 2004). Psychoactive drugs and the medical management of drug‑addicted prisoners Page 71