Psychostimulant modulation of learning and reward

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。

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.