Grace A A
Department of Behavioral Neuroscience, University of Pittsburgh, PA 15260.
Neuroscience. 1991;41(1):1-24. doi: 10.1016/0306-4522(91)90196-u.
A novel mechanism for regulating dopamine activity in subcortical sites and its possible relevance to schizophrenia is proposed. This hypothesis is based on the regulation of dopamine release into subcortical regions occurring via two independent mechanisms: (1) transient or phasic dopamine release caused by dopamine neuron firing, and (2) sustained, "background" tonic dopamine release regulated by prefrontal cortical afferents. Behaviorally relevant stimuli are proposed to cause short-term activation of dopamine cell firing to trigger the phasic component of dopamine release. In contrast, tonic dopamine release is proposed to regulate the intensity of the phasic dopamine response through its effect on extracellular dopamine levels. In this way, tonic dopamine release would set the background level of dopamine receptor stimulation (both autoreceptor and postsynaptic) and, through homeostatic mechanisms, the responsivity of the system to dopamine in these sites. In schizophrenics, a prolonged decrease in prefrontal cortical activity is proposed to reduce tonic dopamine release. Over time, this would elicit homeostatic compensations that would increase overall dopamine responsivity and thereby cause subsequent phasic dopamine release to elicit abnormally large responses.
本文提出了一种调节皮层下区域多巴胺活性的新机制及其与精神分裂症的可能关联。该假说基于多巴胺释放至皮层下区域的调节通过两种独立机制实现：（1）多巴胺神经元放电引起的短暂或相位性多巴胺释放，以及（2）由前额叶皮层传入神经调节的持续性“背景”紧张性多巴胺释放。行为相关刺激被认为会引起多巴胺细胞放电的短期激活，从而触发多巴胺释放的相位成分。相比之下，紧张性多巴胺释放被认为通过其对细胞外多巴胺水平的影响来调节相位性多巴胺反应的强度。通过这种方式，紧张性多巴胺释放将设定多巴胺受体刺激（包括自身受体和突触后受体）的背景水平，并通过稳态机制设定系统对这些部位多巴胺的反应性。在精神分裂症患者中，前额叶皮层活动的长期降低被认为会减少紧张性多巴胺释放。随着时间的推移，这将引发稳态补偿，从而增加整体多巴胺反应性，进而导致随后的相位性多巴胺释放引发异常大的反应。
