Cocaine addicts experience a decrease in D2 receptors affecting brain regions involved with movement, as well as motivation

A new study builds on previous research showing that cocaine-addicted people have a low expression of specific dopamine receptors—D2 receptors—in a portion of the brain called the striatum.

The new findings demonstrate that cocaine-addicted people have decreased D2 receptors in a generalized fashion throughout the various subdivisions of this brain region.

In addition, the researchers found that the decrease in the number of these receptors extended beyond parts of the striatum associated with pleasure or cognition to parts associated with movement. Although the significance of this finding is not known, it was unexpected, the scientists report.

In the study, 17 healthy control subjects and 17 recently detoxified drug-addicted subjects, who reported smoking crack cocaine 4 days per week for about 15 years, underwent positron emission tomography (PET) scanning that allowed the scientists to observe their brain biochemistry.

The D2 receptor is one of five in the brain associated with the chemical dopamine, which is thought to regulate reward and some behaviors, such as sex and eating. Previous research suggests that drugs of abuse activate the brain’s dopamine system. The discharge of dopamine in the brain creates a pleasurable sensation, prompting a craving for more of the substance that triggered its release. The D2 receptor may help power that craving.

The brain scans confirmed that people who are dependent on cocaine have fewer D2 receptors and that this decrease is evident throughout the striatum.

The scientists also hypothesized the decrease in D2 receptors would be associated with maintaining the addictive behavior. However, they found no relationship between the number of these dopamine receptors and the subjects’ perception of cocaine’s pleasurable effects and their drug-seeking behavior.

People who are dependent on cocaine experience a decrease in D2 receptors, but it remains unknown at present if this decrease predisposes someone to be vulnerable to cocaine addiction or if it is a consequence of cocaine exposure. This decrease in D2 receptors also may be more widespread than previously thought, affecting brain regions involved with movement, as well as motivation. Future studies may be warranted to establish the significance of these findings.

Dr. Diana Martinez and her colleagues at Columbia University published this NIDA-funded study in the online March 2004 issue of Neuropsychopharmacology.