Department of Neurochemistry and Neuropharmacology, Institut d'Investigacions Biomèdiques de Barcelona (CSIC), IDIBAPS, Spain.
Int J Neuropsychopharmacol. 2011 Apr;14(3):289-302. doi: 10.1017/S1461145710000349. Epub 2010 Apr 8.
Derangements of the prefrontal cortex (PFC) and of brainstem monoaminergic systems occur in depression and schizophrenia. Anatomical and functional evidence supports a PFC control of the brainstem monoaminergic systems. Similarly, the PFC contains a high density of monoamine receptors for which antipsychotic drugs exhibit high affinity. This raises the possibility that pathological or drug-induced changes in PFC may subsequently alter monoaminergic activity. Recent data indicate that a substantial proportion of PFC pyramidal neurons projecting to the ventral tegmental area (VTA) or the dorsal raphe nucleus (DR) express the 5-HT2A receptor mRNA, which suggests that atypical antipsychotic drugs affect serotonergic and dopaminergic function by targeting PFC 5-HT2A receptors. Using electrophysiological and tract-tracing techniques we examined whether PFC pyramidal neurons projecting to DR are segregated from those projecting to the VTA. Sequential electrical stimulation of these nuclei in anaesthetized rats evoked antidromic potentials from both areas in the same pyramidal neurons of the medial PFC (60%, n=30). A similar percentage of dual DR+VTA projection neurons (50%) was obtained using the reciprocal collision test (n=85). Similarly, tracer application (Fluoro-Gold in VTA and cholera toxin B in DR, or vice versa) retrogradely labelled pyramidal neurons in PFC projecting to VTA (81±18), to DR (52±9) and to both nuclei (31±4, n=5 rats). Overall, these results indicate that the PFC may simultaneously coordinate the activity of dopaminergic and serotonergic systems within a short temporal domain, supporting a concerted modulation of the ascending serotonergic and dopaminergic activity during antipsychotic drug treatment.
前额叶皮层（PFC）和脑干单胺能系统的紊乱发生在抑郁症和精神分裂症中。解剖学和功能证据支持 PFC 对脑干单胺能系统的控制。同样，PFC 含有高密度的单胺受体，抗精神病药物对其具有高亲和力。这就提出了这样一种可能性，即 PFC 的病理性或药物诱导变化可能随后改变单胺能活性。最近的数据表明，投射到腹侧被盖区（VTA）或背侧中缝核（DR）的大量 PFC 锥体神经元表达 5-HT2A 受体 mRNA，这表明非典型抗精神病药物通过靶向 PFC 5-HT2A 受体来影响 5-羟色胺能和多巴胺能功能。使用电生理和追踪技术，我们检查了投射到 DR 的 PFC 锥体神经元是否与投射到 VTA 的锥体神经元分离。在麻醉大鼠中，对这些核进行顺序电刺激，从内侧 PFC 的同一锥体神经元中诱发了来自这两个区域的逆行电位（60%，n=30）。使用相互碰撞测试（n=85）获得了类似比例的双重 DR+VTA 投射神经元（50%）。同样，示踪剂应用（Fluoro-Gold 在 VTA 中，霍乱毒素 B 在 DR 中，反之亦然）逆行标记 PFC 中投射到 VTA（81±18）、DR（52±9）和两个核（31±4，n=5 只大鼠）的锥体神经元。总的来说，这些结果表明，PFC 可能在短时间内同时协调多巴胺能和 5-羟色胺能系统的活动，支持在抗精神病药物治疗期间对上行 5-羟色胺能和多巴胺能活动进行协调调制。
