Rapid dopamine release in nucleus accumbens in Pavlovian-to-Instrumental Transfer

描述（由申请人提供）：动物需要在其环境中寻找奖励刺激，如食物和配偶，因此，必须采取有助于获得这些奖励的行动。此外，与期望结果相关的线索也可以激发目标寻求行为。虽然与食物等“自然”奖励相关的线索可能会激发产生这些结果的行为，但在吸毒成瘾状态下，这可能会成为一种病态，导致即使在戒断一段时间后也会再次吸毒。因此，巴甫洛夫线索可以成为目标寻求工具行为的强大激励因素。通过一项名为巴甫洛夫-工具转移（PIT）的任务，我们可以研究正常大鼠的这种动机行为，并将其作为理解成瘾状态下这种行为的模型。在这项任务中，结果相关的线索已经证明，与线索缺失的基线条件相比，结果相关的线索可靠地增强了习得的工具反应。这项任务已被证明需要伏隔核（NAc）的完整性，特别是伏隔内多巴胺（DA）的作用来调节这一作用。然而，目前尚不清楚DA释放事件如何快速介导PIT效应。利用快速扫描循环伏安法（FSCV）技术，我们建议测量亚秒DA在NAc中的释放，并比较NAc核和壳亚区的这种活性。此外，为了了解DA如何影响PIT中离散事件的神经编码，我们将采用FSCV和电生理技术相结合的方法来测量同一位置的DA释放和神经放电。通过描述PIT中DA释放与NAc编码奖励之间的关系，我们希望为理解复杂联想奖励过程中涉及的神经回路奠定基础。这将为理解幼稚和吸毒状态下动机行为的神经基础提供基础。

DESCRIPTION (provided by applicant): 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.