Psychostimulant modulation of learning and reward

描述（由申请人提供）：该提案探讨了奖励配对刺激对奖励寻求行为的动机控制的神经机制，以及暴露于滥用药物对其的调制。具体来说，本提案探讨了参与的细胞外信号调节激酶（ERK）通路在伏隔核核心（NAcc）的线索控制的行为，以及如何暴露于一种滥用的物质，精神兴奋剂d-苯丙胺，可能会改变NAcc ERK信号改变线索控制的行为。据推测，NAcc ERK信号是必要的奖励配对刺激，以激励奖励寻求行为。此外，假设d-安非他明暴露通过增加NAcc ERK激活来响应奖励配对刺激来增强线索控制行为。拟议的实验使用巴甫洛夫和工具学习任务，再加上颅内输注的ERK拮抗剂，以评估NAcc ERK信号在线索诱导的奖励寻求的作用。将使用蛋白质印迹分析评估d-安非他明暴露对线索诱导的奖赏寻求和线索诱发的ERK激活的影响。这些实验可能揭示了由药物配对线索引起的复发的潜在机制。

DESCRIPTION (provided by applicant): This proposal explores the neural mechanisms underlying motivational control of reward-seeking behavior by reward-paired stimuli, and their modulation by exposure to drugs of abuse. Specifically, this proposal examines the involvement of the extracellular-signal regulated kinase (ERK) pathway in the Nucleus Accumbens core (NAcc) in cue-controlled behavior, and how exposure to one abused substance, the psychostimulant d-amphetamine, may alter cue-controlled behavior by altering NAcc ERK signaling. It is hypothesized that NAcc ERK signaling is necessary for reward-paired stimuli to motivate reward-seeking behavior. Furthermore, d-amphetamine exposure is hypothesized to enhance cue-controlled behavior by increasing NAcc ERK activation in response to reward-paired stimuli. The proposed experiments use Pavlovian and instrumental learning tasks coupled with intracranial infusions of an ERK antagonist to assess the role of NAcc ERK signaling in cue-induced reward seeking. The effect of d-amphetamine exposure on cue-induced reward seeking and cue-evoked ERK activation will be assessed using Western blot analysis. These experiments may shed light on the mechanisms underlying relapse caused by drug-paired cues.