Neurochemical Analysis of Motivated Behavior

非技术总结首席研究员：梅塞尔，R.建议编号：IBN-9723876动机行为的神经化学分析这个项目的长期目标是探索大脑中的化学系统如何控制动机行为。在动机行为中，进食和饮酒等摄食行为构成了这类研究的重点。要制定一般原理来解释动机行为的控制，需要对各种行为(如生殖行为、攻击性)的研究结果。到目前为止，人们对雌性交配行为的动机成分的神经化学知之甚少。我们以仓鼠为实验模型，继续研究表明，中脑边缘多巴胺系统与雌性交配行为的激励(例如，奖励)特性的控制之间存在联系。这项提案中的研究旨在从三个具体方面进一步探讨神经多巴胺通路与女性性行为之间的联系。首先，我们打算继续进行微透析研究，展示女性生殖功能与伏隔核细胞外多巴胺水平之间的密切关系。我们已经证明，与没有经验的雌性仓鼠相比，有经验的雌性仓鼠在与雄性仓鼠的互动中表现出更高、更持久的细胞外多巴胺水平。由于反应敏感化是药物反复激活的多巴胺神经元的一个特性，我们将明确测试经验丰富的雌性仓鼠伏隔核多巴胺水平的增加是否反映了这些神经元对交配遇到的刺激的敏化反应。这将是第一次展示由于表达自然主义行为而导致的多巴胺神经元的敏化。我们的第二个目标是为多巴胺和雌性交配行为之间的关系提供一个更广泛的神经学视角。到目前为止，伏隔核和背侧纹状体是在交配过程中进行体内多巴胺测量的唯一大脑区域。我们打算将这一分析扩展到其他与行为相关的多巴胺能终末区域，如额叶皮质、内侧视前区和杏仁核。在这些实验的背景下，我们将确定这些区域中每一个区域的多巴胺与女性交配行为的表达或与社交相关的其他因素的相关程度。解释这些行为发现的一个关键问题围绕着单个多巴胺能神经元投射到多个靶点的程度。也就是说，每个终端场的多巴胺能活动的相似或不同是否源于相同或不同的多巴胺神经元的活动。对于任何物种来说，这都是一个悬而未决的问题，我们建议定量地确定单个多巴胺神经元支配多个终端场的程度。总之，这些研究将为定义功能性多巴胺能通路如何调控女性生殖行为的不同组成部分提供一个框架，为开发多巴胺在动机行为中的作用的泛化提供基础。

NON-TECHNICAL SUMMARY Principal Investigator: Meisel, R. Proposal Number: IBN-9723876 Neurochemical Analysis of Motivated Behavior The long-term goal of this project is to explore how chemical systems in the brain control motivated behavior. Among motivated behaviors, ingestive behaviors such as feeding and drinking have formed the focus of such studies. To develop general principles to explain the control of motivated behaviors, the results from studies on a variety of behaviors (e.g., reproductive behavior, aggression) are needed. To date, little is known about the neurochemistry of the motivational components of female mating behavior. We have pursued studies showing a link between the mesolimbic dopamine system and the control of the incentive (e.g., reward) properties of female mating behavior, using hamsters as our experimental model. The studies in this proposal are designed to further pursue this link between neural dopamine pathways and female sexual behavior in three specific ways. First, we intend to continue microdialysis studies demonstrating proximal relationships between female reproductive function and extracellular dopamine levels in the nucleus accumbens. We have demonstrated that experienced female hamsters show higher, and more sustained extracellular dopamine levels during interactions with males compared with inexperienced females. As sensitization of responsiveness is one property of dopamine neurons repeatedly activated with drugs, we will explicitly test whether this augmentation of nucleus accumbens dopamine levels in experienced female hamsters reflects a sensitized response of these neurons to stimuli received during mating encounters. This would be the first such demonstration of sensitization of dopamine neurons resulting from the expression of a naturalistic behavior. Our second goal is to provide a broader neurological perspective on the relationship be tween dopamine and female mating behavior. To date, the nucleus accumbens and dorsal striatum are the only brain regions in which in vivo measurements of dopamine during mating encounters have been taken. We intend to extend this analysis to other behaviorally-relevant dopaminergic terminal fields, such as the frontal cortex, medial preoptic area, and amygdala. In the context of these experiments we will determine the degree to which dopamine in each of these areas is related to the expression of female mating behavior or some other factor associated with social encounters. A key issue in the interpretation of these behavioral findings centers around the degree to which individual dopaminergic neurons project to multiple targets. That is, do similarities or differences in dopaminergic activity in each terminal field derive from the activity of the same or different dopamine neurons. This is an unresolved issue for any species, and we propose to determine quantitatively the degree to which individual dopamine neurons innervate multiple terminal fields. Together these studies will provide a framework for defining how functional dopaminergic pathways regulate different components of female reproductive behavior, providing a basis for developing generalizations of the role of dopamine in motivated behavior.