Animals are required to seek out rewarding stimuli in their environment such as food and mates, and as such, must perform actions that will help them obtain those rewards. In addition, cues associated with desired outcomes can also motivate goal-seeking behavior. While cues associated with "natural" rewards like food may invigorate actions that will produce those outcomes, this can become pathologial in the drug addicted state, leading to relapse in drug taking even after a period of abstinence. Thus, Pavlovian cues can be powerful motivators of goal-seeking instrumental behavior. Employing a task called Pavlovian-to- lnstrumental Transfer (PIT), we can investigate this motivated behavior in normal rats and use it as a model for understanding this behavior in the addicted state. In this task, it has been demonstrated that outcome- associated cues reliably potentiate learned instrumental responses compared to baseline conditions where the cues are absent. This task has been shown to require the integrity of the nucleus accumbens (NAc), and specifically, the action of intra-accumbal dopamine (DA) to mediate this effect. However, it is currently unknown how rapid DA release events mediate the PIT effect. Using a technique known as fast scan cyclic voltammetry (FSCV), we propose to measure subsecond DA release in NAc, and compare such activity in the NAc core and shell subregions. Further, to understand how DA may influence neural encoding of discrete events in PIT, we will then employ a combined FSCV and electrophysiology technique that will allow measurement of simultaneous DA release and neural firing at the same location. In describing the relationship between DA release and NAc encoding of reward during PIT, we hope to develop the foundation for understanding the neurocircuitry involved in complex associative reward processes. This will provide a basis for understanding the neural basis of motivated behavior in both the naive and drug- addicted state. PUBLIC HEALTH: Drug addiction exacts a heavy burden on individuals and their social environments. Many addicted people are able to stop drug consumption for long periods only to relapse some time later. These bouts are often triggered by salient drug-associated cues. Understanding both the behavioral and neurobiological basis of how these cues come to take control of learned behaviors is thus of utmost importance in developing pharmacological treatments in humans.
|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|
|Cerri, Domenic H; Saddoris, Michael P; Carelli, Regina M (2014) Nucleus accumbens core neurons encode value-independent associations necessary for sensory preconditioning. Behav Neurosci 128:567-78|
|Saddoris, Michael P; Stamatakis, Alice; Carelli, Regina M (2011) Neural correlates of Pavlovian-to-instrumental transfer in the nucleus accumbens shell are selectively potentiated following cocaine self-administration. Eur J Neurosci 33:2274-87|