The ability of an animal to alter behavior in response to changes in their environment is necessary for survival. Patients with neuropsychiatric disorders, especially addictive disorders, often have difficulty with this type of behavioral flexibility. One can measure the ability of an animal to alter goal-directed behavior following a change in outcome value using a reinforcer devaluation task. In this task, animals form associations between stimuli (e.g. cue) and specific reinforcer(s) (e.g. food rewards). The reinforcer is subsequently """"""""devalued"""""""" by selective satiation (providing the food ad libitum). Following devaluation, normal subjects adjust their responding which reflects the new """"""""value"""""""" of the reinforcer in the absence of new associative learning. The nucleus accumbens (NAc), in conconjuction with several other brain structures (e.g., orbitofrontal cortex and basolateral amygdala), is necessary for behavioral flexibly as measured by reinforcer devaluation tasks. However, it is unknown how DA input from the ventral tegmental area (VTA) to the NAc encodes goal-directed behavior following devaluation in """"""""real-time,"""""""" or how manipulations of DA release can modulate this behavior. In order to assess this, two Specific Aims are proposed to address these issues.
Aim 1 is designed to use electrochemical methods (fast scan cyclic voltammetry) to measure rapid DA signaling in the NAc core and shell to reward predictive cues and responses following reward devaluation.
Aim 2 will use optogenetic manipulations to artificially stimulate DA release in NAc during acquisition or expression of the reinforcer devaluation task. Understanding the neural circuitry underlying flexible goal-directed behavior will help elucidate neural impairments in patients with neuropsychiatric disorders. As such, the proposed studies will provide critical insight into potentially new and more selective target systems for therapeutic intervention for individuals with maladaptive reward seeking, a hallmark of drug addiction.
Patients suffering from addictive disorders are impaired in their ability to alter behavior in response to negative consequences. In an effort to understand maladaptive decision making that contributes to addictive behaviors, we must first understand the underlying neurobiological mechanisms of normal decision making, specifically, the ability of subjects to alter behavior based on changing outcomes. This proposal aims to examine the neurochemical mechanisms underlying flexible behavior which will provide crucial information for potential treatments of drug addiction.
|Haake, Rachel M; West, Elizabeth A; Wang, Xuefei et al. (2018) Drug-induced dysphoria is enhanced following prolonged cocaine abstinence and dynamically tracked by nucleus accumbens neurons. Addict Biol :|
|Hurley, Seth W; West, Elizabeth A; Carelli, Regina M (2017) Opposing Roles of Rapid Dopamine Signaling Across the Rostral-Caudal Axis of the Nucleus Accumbens Shell in Drug-Induced Negative Affect. Biol Psychiatry 82:839-846|
|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|