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ENDORPHINS AND BRAIN REWARD MECHANISMS

内啡肽和大脑奖励机制

基本信息

批准号：
3213099
负责人：
ELLIOT A STEIN
金额：
$ 11.71万
依托单位：
MEDICAL COLLEGE OF WISCONSIN
依托单位国家：
美国
项目类别：
财政年份：
1989
资助国家：
美国
起止时间：
1989-07-01 至 1993-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3213099
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

项目摘要

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加强，它们就会学习执行行为当这样做的时候。然而，并不是所有的奖励都会导致可以接受的行为一种文化，例如寻求毒品的行为。因此，获得一个更好地了解大脑奖赏的解剖和神经化学机制，因为它的启发式和实用价值。数不胜数研究大脑奖励的实验模型已经开发出来，包括自我管理、地点偏好和脑刺激 (ICS)。大多数人都专注于单一的医疗模式。这个项目是旨在通过以下方式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服从于奖励和奖励的行为反应的表达讨厌的环境刺激。内源性阿片肽已经被被牵连为这些刺激的调停者。为此，在活体内阿片受体放射自显影(受体占有率和因此，一个内啡肽能活性的标记物)被提出。这将是提供强化行为过程中大脑阿片类药物活动的“快照” 并验证是否存在特定的化学/解剖电路产生并维持奖励行为。具体地说，动物将是经过培训，以应对ICSM，无论是否叠加环境应激源--足部电击。阿片类药物的双重性质镇痛和奖赏暗示了大脑机制之间的密切关系处理这些品质。对于一个有机体来说，要在它的环境中，必须持续地对环境线索的相对情感性质。这样做的目的是项目是检查发生的神经化学和解剖学变化而动物则会做出这样的行为。这方面的长期目标项目是假设大脑机制的新颖性和/或报酬的共性。这可能会导致人们对滥用药物对这个假定的奖赏回路的影响程度，可能会导致更好的理解和药物修饰或阻断他增强兴奋剂、鸦片类药物、酒精、等等，其可以在接收器级别(即，纳曲酮)或通过干预与药物无关的“奖赏”部位直接行动地点。