Tonic and Phasic Glutamate Release in Incentive Salience and Cocaine Reinforcement

The proposed career development plan is designed to provide the PI with a unique skill set and experience to meet the short-term goal of becoming a productive, independent researcher and long-term goal of becoming a significant contributor to the understanding and treatment of substance abuse disorders. The plan will be carried out at the University of Kentucky, an institution with a rich history of interdisciplinary substance abuse research. The PI will be mentored by Dr.Michael Bardo and co-mentored by Dr. Greg Gerhardt, established experts in neuropsychopharmacology and neurochemistry, respectively. The plan proposes to use enzyme-based microelectrode arrays to uncover the role of sub-second tonic/phasic mesocorticolimbic glutamate release in individual differences in incentive salience/value attribution to reward-related cues and cocaine reinforcement in a preclinical rat model. When a stimulus reliably predicts reward, some animals attribute incentive value to the stimulus, and thus will approach and contact it (sign-trackers); other animals use the stimulus as a simple signal of forthcoming reward, and thus will approach the receptacle into which reward will be delivered (goal-trackers). Recently, it has been demonstrated that differences in sign and goal tracking are related to novelty seeking, impulsivity, initial vulnerability to cocaine reinforcement, and relapse vulnerability. In addition to mesocorticolimbic dopamine, stimulus-reward learning and drugs of abuse are known to alter mesocorticolimbic glutamate signaling.