Department of Chemistry, University of Virginia, Charlottesville, Virginia 22901, United States.
ACS Chem Neurosci. 2021 Dec 1;12(23):4371-4379. doi: 10.1021/acschemneuro.1c00175. Epub 2021 Nov 16.
Transient changes in adenosine and dopamine have been measured but no studies have examined if these transient changes occur simultaneously. In this study, we characterized spontaneous adenosine and dopamine transients in anesthetized mice, examining coincident release in the caudate-putamen for the first time. We found that in C57B mice, most of the dopamine transients (77%) were coincident with adenosine, but fewer adenosine transients (12%) were coincident with a dopamine transient. On average, the dopamine transient started 200 ms before its coincident adenosine transient, so they occurred concurrently. There was a positive correlation ( = 0.7292) of adenosine and dopamine concentrations during coincident release. ATP is quickly broken down to adenosine in the extracellular space, and the coincident events may be due to corelease, where dopaminergic vesicles are packaged with ATP, or cotransmission, where ATP is packaged in different vesicles released simultaneously with dopamine. The high frequency of adenosine transients compared to that of dopamine transients suggests that adenosine is also released from nondopaminergic vesicles. We investigated how A and A adenosine receptors regulate adenosine and dopamine transients using A and AKO mice. In AKO mice, the frequency of adenosine and dopamine transients increased, while in AKO mice, the frequency of adenosine alone increased. Adenosine receptors modulate coincident transients and could be drug targets to modulate both dopamine and adenosine release. Many spontaneous dopamine transients have coincident adenosine release, and regulating adenosine and dopamine cotransmission could be important for designing treatments for dopamine diseases, such as Parkinson's or addiction.
腺苷和多巴胺的瞬时变化已经被测量到，但还没有研究检查这些瞬时变化是否同时发生。在这项研究中，我们在麻醉小鼠中描述了自发的腺苷和多巴胺瞬变，首次检查了尾壳核中的同时释放。我们发现，在 C57B 小鼠中，大多数多巴胺瞬变（77%）与腺苷同时发生，但只有较少的腺苷瞬变（12%）与多巴胺瞬变同时发生。平均而言，多巴胺瞬变在与其同时发生的腺苷瞬变前 200 毫秒开始，因此它们是同时发生的。在同时释放时，腺苷和多巴胺的浓度之间存在正相关（ = 0.7292）。在细胞外空间中，ATP 很快被分解为腺苷，同时发生的事件可能是由于共释放引起的，即多巴胺能囊泡与 ATP 一起包装，或者是由于共传递引起的，即 ATP 与同时释放的多巴胺一起包装在不同的囊泡中。与多巴胺瞬变相比，腺苷瞬变的高频发生表明，腺苷也从非多巴胺能囊泡中释放。我们使用 A 和 AKO 小鼠研究了 A 和 A 型腺苷受体如何调节腺苷和多巴胺瞬变。在 AKO 小鼠中，腺苷和多巴胺瞬变的频率增加，而在 AKO 小鼠中，只有腺苷的频率增加。腺苷受体调节同时发生的瞬变，并且可以成为调节多巴胺和腺苷释放的药物靶点。许多自发的多巴胺瞬变伴随着腺苷的释放，调节腺苷和多巴胺的共传递可能对设计治疗多巴胺疾病（如帕金森病或成瘾）的方法非常重要。
