Molecular and Behavioral Neuroscience Institute, Department of Psychiatry, University of Michigan, Ann Arbor, Michigan 48109, USA.
J Neurosci. 2012 Oct 31;32(44):15369-76. doi: 10.1523/JNEUROSCI.2521-12.2012.
Neural systems that identify and respond to salient stimuli are critical for survival in a complex and changing environment. In addition, interindividual differences, including genetic variation and hormonal and metabolic status likely influence the behavioral strategies and neuronal responses to environmental challenges. Here, we examined the relationship between leptin allelic variation and plasma leptin levels with DAD2/3R availability in vivo as measured with [(11)C]raclopride PET at baseline and during a standardized pain stress challenge. Allelic variation in the leptin gene was associated with varying levels of dopamine release in response to the pain stressor, but not with baseline D2/3 receptor availability. Circulating leptin was also positively associated with stress-induced dopamine release. These results show that leptin serves as a regulator of neuronal function in humans and provides an etiological mechanism for differences in dopamine neurotransmission in response to salient stimuli as related to metabolic function. The capacity for leptin to influence stress-induced dopaminergic function is of importance for pathological states where dopamine is thought to play an integral role, such as mood, substance-use disorders, eating disorders, and obesity.
识别和响应显著刺激的神经系统对于在复杂多变的环境中生存至关重要。此外，个体间差异，包括遗传变异、激素和代谢状态，可能会影响对环境挑战的行为策略和神经元反应。在这里，我们研究了瘦素基因等位变异与血浆瘦素水平与 DAD2/3R 可用性之间的关系，这是通过 [(11)C]raclopride PET 在基线和标准化疼痛应激挑战期间测量得出的。瘦素基因的等位变异与对疼痛应激的多巴胺释放水平的变化有关，但与基线 D2/3 受体可用性无关。循环瘦素也与应激诱导的多巴胺释放呈正相关。这些结果表明，瘦素是人类神经元功能的调节剂，并为代谢功能相关的显著刺激反应中多巴胺神经传递的差异提供了一种病因机制。瘦素影响应激诱导的多巴胺能功能的能力对于那些被认为发挥重要作用的病理状态很重要，例如情绪、物质使用障碍、饮食障碍和肥胖症。
