Although neuroscientists have made considerable progress investigating and characterizing the brain regions that are involved in addiction, the integration of this information with clinical practice is still in its infancy. The neurobiology of addiction addresses the dynamic interaction between addictive drugs and the brain, ranging from drug intoxication to chronic neuroadaptations such as withdrawal, tolerance and craving. While psychological, psychosocial and environmental factors play important roles, addiction is primarily a brain disease (Leshner & Koob, 1999), and a greater understanding of its neurobiology should uncover new and effective treatments. Currently, there is an urgent need for medications capable of reducing craving and recidivism, perhaps by reversing brain disruptions associated with chronic substance abuse. Aside from refining treatment, addiction research has also shed light on the brain's reward centres that so dominate our lives. These centres have evolved over millions of years to reinforce feeding, mating, and other survival-related activities. Tampering with brain reward circuitry, through the process of addiction, produces many of the dangerous and lethal consequences that are associated with addictive illness.

Through the development of technological advances, scientists have developed sophisticated probes into the brain regions that are involved in drug reward. Addictive agents affect different neurotransmitter systems at various anatomical sites, creating distinct ‘fingerprints’ on the reward circuitry. However, the administration of all addictive substances increases extracellular dopamine (DA) levels in the nucleus accumbens (NAc), a location that has been named the ‘universal addiction site’. This remarkable fact will be our starting point in a discussion of pathways that interconnect the midbrain, limbic system, and medial prefrontal cortex (PFC). Repeated administration of addictive drugs often produces opposite brain effects, and evidence of impaired DA neurotransmission has been reported with chronic cocaine, opiate, alcohol and marijuana exposure. Other neuroadaptations have also been identified and will be reviewed, by substance, in an attempt to integrate brain mechanisms with clinical phenomena such as drug withdrawal, craving and progression.

The nature of addiction

The hallmark of addiction is a progressive loss of control over drug intake, regardless of negative consequences. The willingness of drug addicts to risk death, disease, incarceration, job loss, financial ruin and family strife may seem counterintuitive. However, when the dynamics of addiction are understood, the lack of control exhibited by drug addicts becomes more comprehensible.