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）：该提案探讨了通过奖励对刺激对寻求奖励行为的动机控制的神经机制，以及通过暴露于滥用药物的调节。具体而言，该提案研究了细胞信号调节的激酶（ERK）途径在提示控制的行为中的介入核（NACC）中的参与，以及一种滥用物质，心理刺激性d-原甲胺的暴露方式如何通过改变提示控制的行为来改变Cue控制的nAC ERK Cynecc eRK Cynemcc nac Crignal nac Cyndering。假设NACC ERK信号传导是奖励对刺激激励寻求奖励行为所必需的。此外，假设D-苯丙胺暴露是通过响应奖励对刺激来增加NACC ERK激活来增强提示控制的行为。拟议的实验使用帕夫洛维亚人和工具性学习任务以及ERK拮抗剂的颅内输注来评估NACC ERK信号在提示引起的奖励寻求方面的作用。 D-苯丙胺暴露对提示引起的奖励寻求和提示诱发的ERK激活的影响将使用蛋白质印迹分析进行评估。这些实验可能会阐明由药物提示引起的复发机制。

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