Neurochemical Analysis of Motivated Behavior

项目负责人：Meisel， R.提案号：IBN-9723876动机行为的神经化学分析该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，进食和饮水等摄食行为成为这类研究的重点。为了建立解释动机行为控制的一般原则，需要对各种行为（如生殖行为、攻击行为）的研究结果。迄今为止，关于女性交配行为的动机成分的神经化学知之甚少。我们利用仓鼠作为实验模型，研究了中脑边缘多巴胺系统与雌性交配行为的激励（如奖励）特性的控制之间的联系。本提案中的研究旨在通过三种具体方式进一步探索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，证明女性生殖功能与伏隔核细胞外多巴胺水平之间的近端关系。我们已经证明，与没有经验的雌性相比，有经验的雌性仓鼠在与雄性的互动中表现出更高、更持久的细胞外多巴胺水平。由于反应的敏化是多巴胺神经元被药物反复激活的一个特性，我们将明确测试在有经验的雌性仓鼠中伏隔核多巴胺水平的增加是否反映了这些神经元对交配过程中收到的刺激的敏化反应。这将是首次证明多巴胺神经元的敏化是由自然行为的表达引起的。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，伏隔核和背纹状体是唯一在体内测量交配过程中多巴胺的大脑区域。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端区域，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的多巴胺与女性交配行为的表达或与社会接触相关的其他因素的关系程度。解释这些行为发现的一个关键问题集中在个体多巴胺能神经元投射到多个目标的程度上。也就是说，每个终末场多巴胺能活动的相似或差异是否源于相同或不同的多巴胺神经元的活动。这对任何物种来说都是一个未解决的问题，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节女性生殖行为的不同组成部分提供一个框架，为发展多巴胺在动机行为中的作用的概括提供基础。

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.