Psychostimulant modulation of learning and reward

描述(由申请人提供)：这项提案探索了通过与奖励配对的刺激对寻求奖励行为进行动机控制的潜在神经机制，以及接触滥用药物对其进行调节的机制。具体地说，这项建议研究了伏核核心(NAcc)中的细胞外信号调节激酶(ERK)通路参与线索控制的行为，以及暴露于一种滥用的物质-精神刺激剂d-苯丙胺如何通过改变NAcc ERK信号来改变线索控制的行为。假设NAcc ERK信号是奖赏配对刺激激发奖赏寻求行为所必需的。此外，D-苯丙胺暴露被假设通过增加NAcc ERK的激活来增强线索控制的行为，以响应奖励配对的刺激。该实验使用巴甫洛夫学习任务和工具性学习任务，并结合脑内注射ERK拮抗剂来评估NAcc ERK信号在线索诱导的奖赏寻求中的作用。D-苯丙胺暴露对线索诱导的奖赏寻求和线索诱发的ERK激活的影响将通过Western印迹分析来评估。这些实验可能会阐明药物配对线索导致复发的潜在机制。

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.