Nativio Paola, Zoratto Francesca, Romano Emilia, Lacivita Enza, Leopoldo Marcello, Pascale Esterina, Passarelli Francesca, Laviola Giovanni, Adriani Walter
Departments of Molecular Medicine and of Medical Surgical Sciences and Biotechnology, "Sapienza" University of Rome, Rome, Italy.
Department of Cell Biology and Neurosciences, Istituto Superiore Di Sanità, Rome, Italy.
Synapse. 2015 Nov;69(11):533-42. doi: 10.1002/syn.21846. Epub 2015 Sep 14.
Brain serotonin 7 (5-HT7) receptors play an important functional role in learning and memory, in regulation of mood and motivation, and for circadian rhythms. Recently, we have studied the modulatory effects of a developmental exposure (under subchronic regimen) in rats with LP-211, a brain-penetrant and selective 5-HT7 receptor agonist. We aimed at further deciphering long-term sequelae into adulthood. LP-211 (0.250 mg/kg i.p., once/day) was administered for 5 days during the adolescent phase (postnatal days 43-45 to 47-49). When adult (postnatal days >70), forebrain areas were obtained for ex vivo immunohistochemistry, whose results prompted us to reconsider the brain connectivity maps presented in our previous study (Canese et al., Psycho-Pharmacol 2015;232:75-89.) Significant elevation in levels of 5-HT7 receptors were evidenced due to adolescent LP-211 exposure, in dorsal striatum (which also shows an increase of dopaminergic D2 auto-receptors) and-unexpectedly-in piriform cortex, with no changes in ventral striatum. We observed that functional connectivity from a seed on the right hippocampus was more extended than reported, also including the piriform cortex. As a whole, the cortical loop rearranged by adolescent LP-211 exposure consisted in a hippocampus receiving connections from piriform cortex and dorsal striatum, the latter both directly and through functional control over the 'extended amygdala'. Such results represent a starting point to explore neurophysiology of 5-HT7 receptors. Further investigation is warranted to develop therapies for sleep disorders, for impaired emotional and motivational regulation, for attentive and executive deficit. The 5-HT7 agonist LP-211 (0.250 mg/kg i.p., once/day) was administered for 5 days during adolescence (postnatal days 43-45 to 47-49) in rats. When adult (postnatal days >70), a significant elevation in levels of 5-HT7 receptors were evidenced in dorsal striatum and-unexpectedly-in piriform cortex.
脑血清素7（5-HT7）受体在学习与记忆、情绪和动机调节以及昼夜节律方面发挥着重要的功能作用。最近，我们研究了发育暴露（亚慢性给药方案）对大鼠的调节作用，使用的是LP-211，一种可穿透血脑屏障的选择性5-HT7受体激动剂。我们旨在进一步解读成年后的长期后遗症。在青春期（出生后第43 - 45天至47 - 49天），每天腹腔注射一次LP-211（0.250毫克/千克），持续5天。成年后（出生后第70天以上），获取前脑区域用于离体免疫组织化学分析，其结果促使我们重新审视我们之前研究中呈现的脑连接图谱（卡内塞等人，《精神药理学》，2015年；232:75 - 89）。青春期暴露于LP-211后，背侧纹状体（其多巴胺能D2自身受体也增加）以及出人意料的梨状皮质中5-HT7受体水平显著升高，腹侧纹状体则无变化。我们观察到，来自右侧海马体一个种子点的功能连接比报道的更为广泛，还包括梨状皮质。总体而言，青春期LP-211暴露重新排列的皮质环路包括一个接收来自梨状皮质和背侧纹状体连接的海马体，背侧纹状体既直接连接，又通过对“扩展杏仁核”的功能控制进行连接。这些结果是探索5-HT7受体神经生理学的一个起点。有必要进一步研究以开发针对睡眠障碍、情绪和动机调节受损、注意力和执行功能缺陷的治疗方法。在大鼠青春期（出生后第43 - 45天至47 - 49天），每天腹腔注射一次5-HT7激动剂LP-211（0.250毫克/千克），持续5天。成年后（出生后第70天以上），背侧纹状体以及出人意料的梨状皮质中5-HT7受体水平显著升高。
