Neurobiology and principles of addiction and tolerance

Substances of abuse dysregulate the major pathways underlying aspects of motivation, reward, decision-making and memory. As drug use evolves from an impulsive to compulsive action, the brain undergoes neuro-adaptation, during which there is a shift in the importance of different neurotransmitters. Dopamine plays an important role in addiction, providing initial pleasure to a drug, or a positive reinforcing drug effect that leads subsequently to motivation and drug seeking. As an individual becomes tolerant, there is a shift away from dopaminergic pathways towards the involvement of excitatory glutamatergic pathways. Although addiction can be observed for all drugs of abuse, the underlying neurotransmitters and adaptions can vary between drugs. This review focuses on the neurobiology of addiction and tolerance for alcohol, benzodiazepines, opioids, and stimulants.