Neurobiology and principles of addiction and tolerance

Substances of abuse dysregulate key brain systems involved in motivation, reward, decision-making and memory. As drug use evolves into a compulsive addiction, there are adaptations in these systems, mediated by a number of different neurotransmitters. The mesolimbic dopaminergic pathway plays a central role in the pleasurable and positive reinforcing effects of drugs. As an individual becomes addicted, there is a shift away from this positive reinforcement to the compulsive, habitual drug-seeking behaviours driven, for example, by cravings or withdrawal symptoms.