Development of a GABAergic treatment for substance abuse using PET

Development of an effective treatment for substance abuse relies on a better understanding of the nature of the brain reward circuitry and neurotransmitter systems regulating the mechanisms responsible for drug abuse, addiction, and dependence. The use of positron emission tomography (PET) enables the direct assessment of pharmacokinetic and pharmacodynamic events in vivo. We demonstrated that administration of gamma-vinyl gamma aminobutyric acid (GVG, vigabatrin), acting through potentiation of GABAergic tone, leads to decreases in brain extracellular dopamine concentrations as measured with PET and in vivo microdialysis. This knowledge, combined with the notion that addictive drugs share the ability to stimulate dopaminergic neurotransmission, suggests a novel GABAergic strategy for the treatment of substance abuse. Over the past several years PET and in vivo microdialysis, combined with an array of behavioral tests, have demonstrated the potential utility of this approach. Taken together, our data support the use of vigabatrin for the treatment of multiple drug addictions. (C) 2003 Wiley-Liss, Inc.