Commentary in 2005

One of the most difficult problems in treating addiction is not withdrawing addicts from drugs, but preventing relapse. Persistent neuroadaptations are thought to underlie aspects of addiction, including relapse. This commentary assesses the degree to which these neuroadaptations, primarily identified in preclinical studies on cocaine, induce relapse.

Although many drug-induced neural changes are known, progress has been slow in identifying the ones that actually mediate addiction. Identifying changes that are specific to particular elements of the transition from initial to habitual to relapsing drug use may be a fruitful strategy for pinpointing which forms of drug-induced plasticity are critical for addiction.

Drug seeking is associated with activation of reward neural circuitry. Here we argue that drug addiction also involves a 'dark side'—a decrease in the function of normal reward-related neurocircuitry and persistent recruitment of anti-reward systems. Understanding the neuroplasticity of the dark side of this circuitry is the key to understanding vulnerability to addiction.

In the United States, efforts to treat addiction are hampered by prejudice and a public view that treats it as a disorder of self-control, not a disease. We highlight select advances in addiction research that, if disseminated to the public, could reverse these misconceptions and facilitate changes in policy to improve treatment access and care delivery for this highly prevalent disease.

Long-term potentiation and long-term depression require postsynaptic depolarization, which many current models attribute to backpropagating action potentials. New experimental work suggests, however, that other mechanisms can lead to dendritic depolarization, and that backpropagating action potentials may be neither necessary nor sufficient for synaptic plasticity in vivo.

To the degree that drugs and food activate common reward circuitry in the brain, drugs offer powerful tools for understanding the neural circuitry that mediates food-motivated habits and how this circuitry may be hijacked to cause appetitive behaviors to go awry.