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理解取得了重大进展。我之前的研究使用行为药理学来证明多巴胺（DA）在伏隔核（NAc）壳内的传递对配对键合至关重要。具体来说，我的工作表明，在成对键形成过程中，DA浓度的增加足以激活高亲和力的d2样受体，但不能激活低亲和力的d样受体。相反，我之前的行为药理学数据也表明，配对键的维持必须与能够激活d1样受体的高浓度相性DA释放事件有关。因此，药理学研究表明，社会行为中特定的DA传递动态可能调节配对行为。然而，由于没有草原实验室有能力测量实时DA传播动态，我们对社会结合过程中体内DA传播的理解相当有限。在这里，我们将采用快速扫描循环伏安法（FSCV）首次提供亚秒测量草原田鼠NAc壳（和核心）内DA浓度在已知特定DA受体亚型调节的社会相互作用期间的波动。这些研究将验证DA调节配对键合行为是由突触前或突触后机制介导的假设。拟议研究的结果有望在理解社会依恋的神经生物学方面取得重大进展。此外，由于草原田鼠的配对关系在行为学上代表了一种合理的动机行为和动机学习形式，因此这些研究对我们对激励动机、奖励学习的神经科学的总体理解也将具有重要意义，因此，这些研究对我们了解与中脑边缘DA传导调节的社会/动机行为障碍相关的心理障碍也将具有重要意义。

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.