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 reinforcing effects of drugs and the development of addiction. As addiction develops, there is a shift away from positive reinforcement to compulsive, habitual drug-seeking behaviours driven, for example, by craving or aversive withdrawal symptoms. Although the potential for addiction is common to many drugs, the underlying mechanisms, neurotransmission systems and adaptations vary between drugs. This review focuses on the neurobiology of addiction and tolerance for substances including alcohol, benzodiazepines, opioids and stimulants.