ENDORPHINS AND BRAIN REWARD MECHANISMS

内啡肽和大脑奖励机制

• 批准号: 3213096
• 负责人: ELLIOT A STEIN
• 金额: $ 12.78万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-07-01 至 1992-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3213096
• 关键词: autoradiography; brain metabolism; drug abuse; electrostimulus; endorphins; environmental stressor; ethology; laboratory rat; neuroanatomy; neurochemistry; opiate alkaloid; opioid receptor; psychological reinforcement; receptor binding; reinforcer

Animals learn to perform behaviors if they are appropriately reinforced when doing so. However, not all rewards lead to behaviors acceptable to a culture, e.g., drug-seeking behavior. It is thus critical to obtain a better understanding of the anatomy and neurochemistry of brain reward mechanisms, both for its heuristic as well as practical value. Numerous experimental models for studying brain reward have been developed, including self-administration, place preference and brain stimulation (ICS). Most have concentrated on a single modality. This project is designed to bridge the gap between brain chemistry and behavior by providing insights into the anatomic and neurochemical mechanisms subserving the expression of behavioral responses to rewarding and aversive environmental stimuli. Endogenous opioid peptides have been implicated as mediators of these stimuli. To this end, in vivo autoradiography of opiate receptors (a measure of receptor occupancy and thus a marker of endorphinergic activity) is being proposed. This will provide a "snapshot' of brain opiate activity during reinforced behaviors and verify the existence of specific chemical/anatomic circuits which engender and maintain reward behavior. Specifically, animals will be trained to respond for ICSm with or without superimposition of an environmental stressor--footshock. The dual properties of opioids in analgesia and reward implies a close relation between brain mechanisms processing these qualities. For an organism to survive in its environment, continuous discriminations must be performed about the relative affective qualities of environmental cues. The aim of this project is to examine the neurochemical and anatomic changes which occur while an animal performs such behaviors. Long-term objectives of this project are to postulate brian mechanisms of the novelty and/or commonality of reward. This may then lead to speculations about the level at which abused drugs impact on this putative reward circuitry, leading perhaps to better understanding and pharmacologic modification or interruption of he reinforcing efficacy of stimulants, opiates, alcohol, etc., which might be directed either at the receptor level (i.e., naltrexone) or by intervening at "reward" sites independent of the drug's direct sites of action.

如果动物得到适当的强化，它们就会学会执行行为 这样做时。 然而，并非所有的奖励都会导致人们可以接受的行为 一种文化，例如寻求毒品的行为。 因此，获得一个 更好地理解大脑奖励的解剖学和神经化学 机制，既具有启发性又具有实用价值。 很多的 研究大脑奖励的实验模型已经开发出来， 包括自我管理、位置偏好和大脑刺激 （工业控制系统）。 大多数都集中在单一模式上。 这个项目是 旨在弥合大脑化学和行为之间的差距 提供对解剖学和神经化学机制的见解 促进对奖励和行为反应的表达 厌恶的环境刺激。 内源性阿片肽 被认为是这些刺激的中介。 为此，体内 阿片受体放射自显影（受体占用和吸收的测量） 因此，有人提出了内啡肽活性的标记。 这将 提供强化行为期间大脑阿片类药物活动的“快照” 并验证特定化学/解剖回路的存在 产生并维持奖励行为。具体来说，动物将 接受培训以响应 ICSm，有或没有叠加 环境应激源——足部休克。 阿片类药物的双重特性 镇痛和奖赏暗示大脑机制之间存在密切关系 处理这些品质。 有机体要在其生存环境中生存 环境中，必须持续进行歧视 环境线索的相对情感品质。 此举的目的 项目是检查发生的神经化学和解剖学变化 而动物会做出这样的行为。 本次活动的长期目标 项目是假设新颖性和/或的布赖恩机制 奖励的共性。 这可能会引发人们的猜测 滥用药物对这个假定的奖励回路的影响程度， 也许会导致更好的理解和药理学修改或 中断兴奋剂、阿片类药物、酒精、 等等，这可能是针对受体水平（即， 纳曲酮）或通过独立于药物的“奖励”位点进行干预 直接作用部位。