Grant: Operating Grant

Both human imaging and animal models has emphasized the importance of the middle part of the frontal cortex in addiction. Lesions of the medial frontal cortex in animals can greatly reduce the propensity to relapse, while in humans surgically precise lesions of a specific part of the medial frontal cortex (called anterior cingulotomies) are now used to treat severe addiction as well as obsessive compulsive disorder (OCD). Yet remarkably, no one knows why this works or what exactly this area of the brain contributes to the addiction. One reason for this is the dearth of studies that have looked at the way medial frontal neurons respond to drugs and drug-associated cues following prolonged drug use. Over the last decade we have developed techniques to record large numbers of neurons simultaneously as well as analyze how they change during various behaviors in awake freely moving rats. The present proposal will leverage these powerful tools to test the hypothesis that representations of the drug state as well as drug related cues appear more strongly and with a far greater frequency in ensembles of medial frontal cortex neurons of animals that have had a long history of drug use. In essence we propose to track the obsessive drug-related representations that drive drug seeking.