Stress can be defined as any real or perceived threat to the psychological and physical integrity of anindividual, and despite its short-term adaptive value, can cause behavioral, emotional, cognitive, andimmune changes in affected individuals that are potentially harmful. Furthermore, stress can indirectly leadto other negative health consequences by altering the behavioral strategies of the individuals. For example,it has been demonstrated that stress can lead to poor diet, obesity, and substance abuse. It has beenhypothesized that such maladaptive behaviors might arise as a result of stress-induced weakening of theprefrontal cortical functions. Previous studies of stress-induced changes in prefrontal functions showed thatexcessive dopamine and norepinephrine release in prefrontal cortex contributed to working memoryimpairment. However, the effects of stress on the decision-making functions of the prefrontal cortex have notbeen studied. In particular, impulsive choice is a strong predictor for many addictive behaviors, such assmoking and substance abuse, that are exacerbated by stress. Therefore, the effect of stress on impulsivityand prefrontal functions will be the focus of this project. In the proposed study, impulsivity will be quantifiedby the animal's tendency to choose a small but immediate reward rather than a large but delayed reward inan inter-temporal choice task. First, it will be tested whether impulsivity is increased by a pharmacologicalstressor, FG7142. Second, the role of dopaminergic and/or noradrenergic pathways in the regulation ofimpulsive choice behavior will be tested using receptor specific agonists and antagonists. Third, we willexamine how these pharmacological manipulations affect the neural process of discounting the value ofdelayed reward by recording the single-neuron activity of neuronal ensembles in the prefrontal cortex withand without the same pharmacological manipulations. Fourth, using the combination of iontophoresis andsingle-neuron recording, it will be tested whether prefrontal functions related to impulsive choice behaviorsare altered by dopamine and norepinephrine through their direct actions on the prefrontal micro-circuitry.Overall, the results from these experiments will provide a critical piece of information regarding the cellularbasis of stress-mediated impairments in adaptive behavioral strategies and normal prefrontal functions, andthereby contribute to the development of new preventive and therapeutic measures against stress-mediateddisease processes.
