When deciding to act organisms evaluate the costs and benefits of performing a behavior to determine the best option to maximize behavioral output. When making these decisions the expected value of performing a task is a key component which biases responses towards the more valuable option available. Importantly, several factors influence reward value including the cost of performing specific tasks, the delay to reinforcement, the probability of reinforcement, and the magnitude of reinforcement. The nucleus accumbens (NAc) and its dopaminergic input from the ventral tegmental area (VTA) appear to be critically involved in these and related processes. The NAc has been shown to be a critical component in the circuitry that underlies motivated behaviors. Specifically the NAc is commonly referred to as a limbic-motor interface as this structure receives input from corticolimbic areas such as the prefrontal cortex, basolateral amygdala, hippocampus, and a dense dopaminergic projection from the VTA. In turn, the NAc integrates this information and impacts behavior through its GABAergic output projections to the ventral pallidum and lateral hypothalamus. Damage to the NAc and the associated dopaminergic projections results in aberrant decision making behavior when organisms are forced to make choices based on behavioral cost, delay to, and the probability of reward. Here, the NAc circuitry underlying risky decision making behavior will be evaluated using a probabilistic discounting task in which operant responses are reinforced on different reward probability and magnitude contingencies. Thus, animals decide between smaller certain (e.g., press one lever for a single food pellet) and larger uncertain rewards (e.g., press a second lever and 50% of the time 2 food pellets will be delivered). Probabilistic discounting tasks have been shown to be good models of risk-taking behavior since they evaluate if animals will choose to take actions associated with uncertain, yet larger reward. Importantly, it has been shown that both the NAc and dopamine activity are critical components of appropriate decision making based on risk. In this application, two Specific Aims are proposed.
Aim 1 will incorporate electrophysiological recording procedures in behaving rats to examine how the NAc encodes risk-based decision making under normal circumstances.
Aim 2 will seek to understand how dopamine may influence the neural encoding of risk-based decision making by employing a technique that will allow measurement of simultaneous dopamine release and neural firing at the same location during risk-based decision making. If NAc firing and phasic dopamine release are coincident during the task, future studies will examine the link between the two using drug inactivation procedures. The results of these studies will provide invaluable insight into the neurocircuitry involved in normal risk-taking behavior and may have implications for the risk-taking involved in drug addiction.

Public Health Relevance

A critical component of drug addiction is aberrant decision making, such that drug users display persistent and compulsive use of drugs and increased risk taking behaviors despite negative consequences. In the effort to understand the aberrant decision making processes that underlie addictive behaviors, we must first understand the underlying biological mechanisms of normal decision making processes, such as risk-taking behavior. This proposal seeks to describe the neural mechanisms underlying risky decision making which will provide key information for the development of treatments for drug addiction in humans.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Predoctoral Individual National Research Service Award (F31)
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Special Emphasis Panel (ZRG1-F02A-J (20))
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Avila, Albert
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University of North Carolina Chapel Hill
Schools of Arts and Sciences
Chapel Hill
United States
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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
Sugam, Jonathan A; Saddoris, Michael P; Carelli, Regina M (2014) Nucleus accumbens neurons track behavioral preferences and reward outcomes during risky decision making. Biol Psychiatry 75:807-816
Sugam, Jonathan A; Carelli, Regina M (2013) Rolling the dice: the importance of mesolimbic dopamine signaling in risky decision making. Neuropsychopharmacology 38:248
Saddoris, Michael P; Sugam, Jonathan A; Cacciapaglia, Fabio et al. (2013) Rapid dopamine dynamics in the accumbens core and shell: learning and action. Front Biosci (Elite Ed) 5:273-88