Real-time dopamine transmission during prairie vole social behavior

描述（由申请人提供）：对一夫一妻制草原田鼠的配对行为的研究使我们对社会依恋的神经生物学的理解取得了很大的进展。我以前的研究已经使用行为药理学来证明多巴胺（DA）在核内的传递对于成对键合是至关重要的。具体来说，我的工作表明，在成对键形成过程中，DA浓度增加的方式足以激活高亲和力D2样受体，但不低亲和力D样受体。相反，我以前的行为药理学数据也表明，对键的维护必须与高浓度阶段性DA释放事件能够激活D1样受体。因此，药理学研究表明，特定的DA传输动力学在社会行为中可能会调节配对行为。然而，因为没有草原实验室曾经有能力测量实时DA传输动态，我们的了解在社会债券在体内DA传输是相当有限的。在这里，我们将采用快速扫描循环伏安法（FSCV），以提供有史以来第一次亚秒级的测量DA浓度波动内的NAC壳（和核心）的草原田鼠在社会互动与已知的特定DA受体亚型的调节。这些研究将验证这一假设，即DA调节对键合行为介导的突触前或突触后机制。这些研究结果有望代表对社会依恋神经生物学理解的重大进展。此外，由于草原田鼠配对结合代表了动机行为和动机学习的一种行为学上合理的形式，这些研究也将对我们对激励动机，奖励学习的神经科学的一般理解具有重要意义，因此与中脑边缘DA传递调节的社会/动机行为障碍相关的心理障碍。

DESCRIPTION (provided by applicant): Studies of pair bonding behavior in the monogamous prairie vole have allowed for excellent advances in our understanding of the neurobiology of social attachment. My previous research has used behavioral pharmacology to demonstrate that dopamine (DA) transmission within the nucleus accumbens (NAc) shell is critical for pair bonding. Specifically, my work suggests that during pair bond formation, DA concentration is increased in a manner sufficient to activate high affinity D2-like receptors but not low affinity D-like receptors. Conversely, my previous behavioral pharmacology data also suggest that pair bond maintenance must be associated with high concentration phasic DA release events capable of activating D1-like receptors. Thus, pharmacological studies suggest that specific DA transmission dynamics during social behavior may regulate pair bonding behavior. However, because no prairie lab has ever had the capability to measure real-time DA transmission dynamics, our understanding of in vivo DA transmission during social bonding are quite limited. Here, we will employ fast-scan cyclic voltammetry (FSCV) to provide the first ever sub-second measurements of fluctuations in DA concentration within the NAc shell (and core) of prairie voles during social interactions with known regulation by specific DA receptor subtypes. These studies will test the hypothesis that DA regulation of pair bonding behavior is mediated by presynaptic or postsynaptic mechanisms. Findings from the proposed studies promise to represent significant advances specifically for understanding the neurobiology of social attachment. Additionally, since prairie vole pair bonding represents an ethologically sound form of motivated behavior and motivational learning, these studies will also be of significant importance to our general understanding of the neuroscience of incentive motivation, reward learning, and therefore psychological disorders associated with impairments in social/motivational behaviors regulated by mesolimbic DA transmission.