Persons addicted to cocaine often find that the drug is much less enjoyable after years of use, yet they have great difficulty quitting. A new brain imaging study shows why this may be so and also why extinction-based therapy may not be effective for cocaine users. The study, led by researchers at the Icahn School of Medicine at Mount Sinai in New York City, found that in long-term cocaine users, there is global impairment in the ventromedial prefrontal cortex (VMPFC), an area of the brain that is linked to impulse and self-control. "Our study data suggest that it will be hard for long-time cocaine users to unlearn what once was a positive experience if this 'unlearning' or new learning relies on this brain region to be effective," lead investigator Anna Konova, PhD, who worked on the study while at the Icahn School of Medicine but is now a postdoctoral fellow at the Center for Neural Science at New York University, said in a news release. "There is a strong impetus for extinction-based therapy in addiction, but our findings highlight potential limitations of these existing therapies in their reliance on the VMPFC to achieve therapeutic benefits," senior investigator Rita Z. Goldstein, PhD, director of Mount Sinai's Neuropsychoimaging of Addiction and Related Conditions Program, added. The study was published online September 5 in Addiction Biology. Using fMRI and a three-phase classical conditioning paradigm, the researchers examined neural correlates of extinction learning for drug and pleasant cue associations and the role of the VMPFC in 18 non-treatment-seeking, long-term cocaine users and 15 sociodemographically matched healthy individuals who did not use drugs. Extinction learning is a process by which a new, affectively neutral association replaces an old, affectively arousing association. They observed that the long-term cocaine users had trouble forming and maintaining new associations for stimuli that were previously, although no longer, predictive of both drug-related and non-drug-related outcomes and that this impairment was mediated by the VMPFC. The VMPFC signals in the cocaine-using group did not resemble those of the control group. Extinction learning did not engage the VMPFC to the same degree, which could result in failure in extinction learning, the researchers say. "Our view on this is that extinction-based therapy is unlikely to be effective in cocaine addiction as administered in isolation or in its more traditional form," the investigators told Medscape Medical News. "This stems from our data showing a deficit in the neural circuitry that supports this type of learning. Furthermore, we observed this deficit in two contexts, drug-related and not, suggesting it's not likely to work in most conditions. "We do, however, believe that if extinction-based therapy is combined with other treatments or with cognitive enhancers, it could have utility in cocaine addiction. In addition, modified forms of the therapy that harness the science behind more robust extinction methods may also prove useful. More research is clearly needed to test these additional approaches," they concluded. The study was supported by the National Institute of Drug Abuse. The authors report no relevant financial relationships. Source
