The Influence of Environmental Manipulations on Decision-Making and Dopamine Transmission

Thesis (Ph.D.)--University of Washington, 2021The process of educating responses/decisions and controlling our environment can be seen as true liberty. The environment and organisms within it have a bidirectional relationship: the environment affects our internal state which, in turn, affects how an organism navigates through and influences the environment. Decisions require calculation of economic context and utility, and these choices are affected by a myriad of factors. These factors include, but are not limited to, the number of options available, subjective internal states (e.g., stress, fatigue, if the decision has been made before), energy required, magnitude of the outcome (punishment or reward), time to receive outcome, probability of achieving that outcome, and the subjective perspective of the environment in which the decision is made. Although decision-making is complex, the young field of neuroeconomics has sought to reduce these dimensions and empirically test how organisms can assess the utility of decisions. One of the most intensely studied neural mechanisms for reward-guided choice behavior in mammals is the mesolimbocortical dopamine system. Phasic dopamine release in the ventral striatum (nucleus accumbens) from cells projecting from the ventral tegmental area is thought to serve as a learning signal that caches values from a novel rewarding experience and then to any reward-predictive cues for that reward. Disruptions to this monoaminergic system have been applied to theories analyzing the etiology of many psychiatric disorders, such as Major Depressive Disorder and aberrant habitual behaviors, and the therapeutics designed to manage and ameliorate their associated symptoms. Stress and its biological correlates, via the hypothalamus-pituitary-adrenal axis, have been heavily intertwined with our understanding of these diseases. Consequently, I first aim to understand the interaction of intra-accumbal dopamine or corticotrophin-releasing factor antagonism, chronic stress induction, and economic decision-making. I report that corticotrophin-releasing factor and dopamine act in parallel to affect a concurrent choice, operant conditioning paradigm and that stress augmented the effects of the dopamine (DA) and corticotropin-releasing factor (CRF) antagonists on behaviors that were changed by the drugs. Secondly, I aim to understand how habitual or flexible decision-making in the context of manipulating the effort required to obtain a reward and the reward magnitude influences phasic dopamine release in the nucleus accumbens. Overtraining led to inflexible behavior, a flexible training paradigm reliably led to flexible behavior, and phasic dopamine release reflected reward magnitude, regardless of the animals’ choice behavior. Providing more evidence to address these two questions advances our comprehension about the how environmental stressors and the adaptability of economic decisions influences dopamine transmission within the ventral striatum