To effectively secure resources necessary for survival, animals must learn to evaluate the costs and benefits of their behaviors. The mesolimbic dopamine (DA) system, in particular its projection to the nucleus accumbens (NAc), is uniquely situated to process this type of value-related information. Electrophysiology studies in behaving animals show that DA neurons encode specific characteristics of predicted rewards including the cost of, probability of, delay to, and magnitude of future rewards. Likewise, electrochemistry studies employing fast scan cyclic voltammetry (FSCV) have shown that DA release in the NAc encodes similar distinct features of predicted reward values including response costs, delays, magnitude, and risk. Those studies support the seminal theory by Schultz and colleagues that the mesolimbic DA system serves as a prediction error learning signal and as such plays a key role in decision making related to reward. However, there are several critical issues regarding the role of the mesolimbic DA system, particularly its projection to the NAc, in decision making that remain largely unknown. First, although electrophysiology studies are highly informative, it has been less clear precisely how these neural signals translate into DA release in NAc subregions (core versus shell). Differential DA release dynamics across NAc subregions would indicate that although the mesolimbic DA system is involved in decision making and appear to follow reward prediction theory, distinct functional aspects of this processing exist in target regions of the NAc. Second, although electrophysiology and electrochemistry studies have been highly informative, those approaches provide information that is strictly correlational in nature. Additional studies are needed to determine if rapid DA signaling in the NAc is causally linked with decision making behavior. Finally, numerous studies indicate that exposure to abused substances such as cocaine alter decision making behavior, particularly impulsive choices during delay discounting tasks. However, it is not known if a history of cocaine alters rapid DA release in specific NAc subregions during cues that signal those choices. To resolve these issues, three specific aims are proposed.
Aim 1 will fully characterize rapid DA release dynamics in the NAc core versus shell during decision making tasks involving changes in magnitude, delay and during delay discounting.
Aim 2 will determine if NAc core vs. shell rapid DA release during cues that signal high value options is causally linked to behavioral choices for those options using optogenetic tools.
Aim 3 will build upon prior aims and determine the effects of cocaine self-administration experience on rapid DA release dynamics in the NAc core versus shell during delay discounting. Collectively, the proposed studies will provide unprecedented insight into how mesolimbic DA in key target regions of the NAc encode and control decision making behaviors, and how a history of cocaine can alter decision making, a detrimental consequence of repeated drug use.
Optimal decision making requires organisms to evaluate the costs and benefits of potential choices and this ability is disrupted in numerous psychiatric disorders including ADHD, schizophrenia and drug addiction. The proposed studies are designed to examine how the brain mesolimbic dopamine system encodes and controls normal decision making behaviors, and how a history of cocaine can alter aspects of this processing and lead to impulsive behaviors. The studies are clinically relevant since they can provide insight into ways to help reverse addicts impulsive decisions to select the short-term rewards of continued drug use over long-term benefits (e.g., health, jobs, family) associated with abstinence.
|Moschak, Travis M; Terry, Douglas R; Daughters, Stacey B et al. (2018) Low distress tolerance predicts heightened drug seeking and taking after extended abstinence from cocaine self-administration. Addict Biol 23:130-141|
|Saddoris, Michael P; Sugam, Jonathan A; Carelli, Regina M (2017) Prior Cocaine Experience Impairs Normal Phasic Dopamine Signals of Reward Value in Accumbens Shell. Neuropsychopharmacology 42:766-773|
|Sackett, Deirdre A; Saddoris, Michael P; Carelli, Regina M (2017) Nucleus Accumbens Shell Dopamine Preferentially Tracks Information Related to Outcome Value of Reward. eNeuro 4:|
|West, Elizabeth A; Carelli, Regina M (2016) Nucleus Accumbens Core and Shell Differentially Encode Reward-Associated Cues after Reinforcer Devaluation. J Neurosci 36:1128-39|
|Saddoris, Michael P; Wang, Xuefei; Sugam, Jonathan A et al. (2016) Cocaine Self-Administration Experience Induces Pathological Phasic Accumbens Dopamine Signals and Abnormal Incentive Behaviors in Drug-Abstinent Rats. J Neurosci 36:235-50|
|Saddoris, Michael P; Sugam, Jonathan A; Stuber, Garret D et al. (2015) Mesolimbic dopamine dynamically tracks, and is causally linked to, discrete aspects of value-based decision making. Biol Psychiatry 77:903-911|
|Saddoris, Michael P; Cacciapaglia, Fabio; Wightman, R Mark et al. (2015) Differential Dopamine Release Dynamics in the Nucleus Accumbens Core and Shell Reveal Complementary Signals for Error Prediction and Incentive Motivation. J Neurosci 35:11572-82|
|Schultz, Wolfram; Carelli, Regina M; Wightman, R Mark (2015) Phasic dopamine signals: from subjective reward value to formal economic utility. Curr Opin Behav Sci 5:147-154|
|Saddoris, Michael P; Carelli, Regina M (2014) Cocaine self-administration abolishes associative neural encoding in the nucleus accumbens necessary for higher-order learning. Biol Psychiatry 75:156-64|