Dr. Peter Kalivas
Biographical Information

Project 4 - Are New Pharmacological Therapies for Addiction Hiding in Glutamate Synapses

Over the last decade it has become clear that addiction is in part a disorder in cortical regulation of reward and decision-making processes. Accordingly, focus has been brought to the glutamate projections from the prefrontal cortex to the nucleus accumbens. Employing a variety of technologies we have been using cocaine-addicted animals provided by the NARC animal core facility to determine how cocaine abuse changes the function of excitatory synapses. This includes changes in how glutamate is released from presynaptic terminals and glia, as well as how glutamate signals through its receptors. In the process of this research, we have identified a number of proteins that are changed by cocaine addiction, such as GluR1, the cystine/glutamate exchanger, G-protein regulatory proteins and proteins in the postsynaptic density (Homer and actin). Importantly, we have then identified or constructed drugs or treatments to manipulate these proteins and in some cases have prevented relapse in the reinstatement animal models provided by the NARC animal core. One compound, N-acetylcysteine, is now being tried in cocaine addicts to restore the function of the cysteine/glutamate exchanger.