Research in the Neurobiology of Addiction Research Center (NARC) is organized to efficiently determine the neurobiological basis of cocaine and heroin relapse and identify novel pharmacological treatments for drug addicts. The studies are based first around a rat model of addiction and relapse. Animals are trained to intravenously administer cocaine or heroin, and after a period of abstinence, drug-seeking is induced as an animal model of relapse. Specific goals to be achieved with this model include determining which brain areas and neurotransmitters mediate drug-seeking and the changes in cell genomics and proteomics that underlie the addiction-related alterations in brain function. Through this animal model, the NARC has come to focus predominately on glutamate transmission in the projection from the prefrontal cortex to the nucleus accumbens, and the GABA projection from the accumbens to the ventral pallidum. Also, within these projections, specific signaling events being evaluated are presynaptic glutamate release, intracellular signaling pathways associated with glutamate and dopamine receptor occupation, monoamine transporter systems and proteins located in the postsynaptic density of excitatory synapses. From these NARC experiments, treatments and compounds have emerged that appear to reverse relapse in the animal model, and one such compound, N-acetylcysteine, has moved into a NARC-sponsored clinical trial in cocaine addicts.