On June 22, 1998, ‘Wired for Addiction’ was presented as part of NIDA’s Frontiers in Neuroscience seminar series. The theme of these presentations centered on the neuronal remodeling that emerges after repeated substance use and withdrawal, with particular emphasis on the possibility of altered cognitive function as a consequence of the neural remodeling. Presentations were made by Drs. Ann Graybiel, Tony Grace, John Marshall, Janet
Neisewander, and Regina Carelli, and a summary and discussion was presented by Dr. Steve Grant of NIDA. Brief summaries of two presentations follow.

Chronic exposure to psychomotor stimulants may rewire your brain
Exposure to amphetamine and cocaine induces gene expression in cortico-basal ganglia circuits. Chronic intermittent exposure to the same drugs down-regulates some of the inducible change. After a course of chronic intermittent treatment and withdrawal of the drug, a subsequent challenge with the drug induces new patterns of gene expression in cortico-basal ganglia circuits. The repeated administration and withdrawal of cocaine induces both immediate early gene (lEG) expression after drug challenge in neurons that are not activated acutely, and an increase in the size of the area in which this response in observed. These findings raise the possibility that prolonged exposure to psychomotor stimulants produces enduring changes in brain wiring.

Ann Graybiel, Ph.D., Massachusetts Institute of Technology:

Neuronal interactions within the limbic system of rats: Alteration during amphetamine sensitization
Amphetamine exerts differential actions on neurons in the nucleus accumbens when given acutely versus repeatedly. The studies show that repeated amphetamine administration causes an increase in electrical coupling among nucleus accumbens neurons, which appears to be driven by an increase in prefrontal corticoaccumbens afferent activation. It is proposed that such a condition would lead to alteration of information flow within this system, resulting in a perseverance of behavioral action that may contribute to drug-seeking behavior in humans.

Anthony Grace, Ph.D., University of Pittsburgh