Psychostimulant modulation of learning and reward

学习和奖励的精神刺激调节

• 批准号: 7156643
• 负责人: MICHAEL W SHIFLETT
• 金额: $ 4.88万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7156643
• 关键词: amphetamines; behavior; central nervous system stimulants; conditioning; cues; learning

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.

描述（由申请人提供）：本研究旨在探讨奖励配对刺激对寻求奖励行为动机控制的神经机制，以及滥用药物对其的调节作用。具体来说，本研究探讨了伏核核心（NAcc）细胞外信号调节激酶（ERK）通路在线索控制行为中的作用，以及暴露于一种滥用物质（精神兴奋剂d-安非他明）如何通过改变NAcc ERK信号通路来改变线索控制行为。假设NAcc ERK信号是奖励配对刺激激发寻求奖励行为所必需的。此外，d-安非他明暴露被假设通过增加NAcc ERK在响应奖励配对刺激时的激活来增强线索控制行为。本实验采用巴甫洛夫和工具性学习任务，结合颅内输注ERK拮抗剂来评估NAcc ERK信号在线索诱导的奖励寻求中的作用。d-安非他明暴露对线索诱导的奖赏寻求和线索诱发的ERK激活的影响将采用Western blot分析进行评估。这些实验可能揭示药物配对线索引起复发的潜在机制。

项目成果

Acquisition and performance of goal-directed instrumental actions depends on ERK signaling in distinct regions of dorsal striatum in rats.

目标导向工具性动作的获得和执行取决于大鼠背侧纹状体不同区域的 ERK 信号传导。

• DOI: 10.1523/jneurosci.1778-09.2010
• 发表时间: 2010-02-24
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: Shiflett MW;Brown RA;Balleine BW
• 通讯作者: Balleine BW