Neural Substrates of Drug-Induced Reward Devaluation

药物引起的奖赏贬值的神经基质

• 批准号: 6918774
• 负责人: Anne E. Baldwin
• 金额: $ 4.89万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6918774
• 关键词: NMDA receptors; amygdala; appetite; association learning; behavior test; behavioral /social science research tag; biological signal transduction; cocaine; conditioning; digestion; dopamine; drug abuse; experimental brain lesion; glutamate receptor; histology; laboratory rat; morphine; motivation; neurochemistry; postdoctoral investigator; reinforcer; self medication; suppression; taste; thalamus

DESCRIPTION (provided by applicant): Rats will suppress intake of a saccharin solution that predicts either passively administered or self-administered drugs of abuse. For many years it was believed that drugs of abuse were actually producing a conditioned taste aversion, similar to that induced by lithium chloride. However there is substantial evidence to suggest that the suppressive effects of drugs of abuse are actually caused by a devaluation of the natural reinforcer in anticipation of the more potent drug reward--a reward comparison (Grigson, 1997). Little is known about the neural substrates involved this phenomenon, however recent studies have shown that lesions of the gustatory thalamus disrupt the suppressive effects of passively administered cocaine or morphine. Additionally, the classical conditioning involved in reward comparison suggests the involvement of the amygdala, a region thought to be important for both appetitive and aversive associative learning. The involvement of this region is also supported by anatomical findings of a strong projection from the gustatory pathway to the central nucleus of the amygdala. Using lesion techniques, the proposed experiments will examine the contribution of the gustatory thalamus and central nucleus of the amygdala to the suppressive effects of drugs of abuse (Specific Aim 1). The neurochemical basis of these contributions will then be examined via microinfusion techniques (Specific Aim 2).

描述（由申请人提供）： 大鼠将抑制糖精溶液的摄入量，以预测被动施用或自我管理的滥用药物。多年来，人们认为滥用药物实际上产生了条件味道厌恶，类似于氯化锂诱导的药物。但是，有大量证据表明，滥用药物的抑制作用实际上是由于预期更有效的药物奖励而贬值的天然增强剂造成的 - 奖励比较（Grigson，1997）。关于这种现象的神经底物知之甚少，但是最近的研究表明，味觉丘脑的病变破坏了被动施用的可卡因或吗啡的抑制作用。此外，奖励比较中涉及的经典条件表明，杏仁核的参与，该地区被认为对食欲和厌恶的关联学习都很重要。该区域的参与也得到了从味道途径到杏仁核中央核的强烈投影的解剖学发现。使用病变技术，提出的实验将研究杏仁核的味丘脑和中央核对滥用药物的抑制作用的贡献（特定目标1）。然后将通过微灌注技术检查这些贡献的神经化学基础（特定目标2）。