Abstract:
The 5-hydroxytryptamine 2A (5-HT2A) receptor plays an important role in schizophrenia. The 5-HT2A receptor is also involved in the regulation of prepulse inhibition (PPI) in rodents. The aim of this study was to determine whether selective 5-HT2A receptor agonizts or antagonists may alter PPI in rats and to identify the critical brain regions in which the activity of 5-HT2A receptors regulates PPI. The results showed that infusion of the 5-HT2A receptor agonist TCB-2 into the lateral ventricle disrupted PPI, but the 5-HT2A receptor antagonist M100907 had no such effect. In addition, local infusion of TCB-2 into the nucleus accumbens and ventral pallidum disrupted PPI, whereas the same manipulation in the medial prefrontal cortex, ventral hippocampus, and ventral tegmental area did not disrupt PPI. In conclusion, agonism of 5-HT2A receptors in the ventral pallidum and nucleus accumbens can disrupt PPI. The ventral pallidum and nucleus accumbens are critical brain regions responsible for the regulation of PPI by serotonin. These findings contribute to the extensive exploration of the molecular and neural mechanisms underlying the regulatory effect of 5-HT2A receptor activity on PPI, especially the neural circuits modulated by 5-HT2A receptor activity.
摘要:
5-羟色胺2A(5-HT2A)受体在精神分裂症中起重要作用。5-HT2A受体也参与啮齿动物前脉冲抑制(PPI)的调节。这项研究的目的是确定选择性5-HT2A受体激动剂或拮抗剂是否可以改变大鼠的PPI,并确定5-HT2A受体活性调节PPI的关键大脑区域。结果表明,向侧脑室输注5-HT2A受体激动剂TCB-2破坏了PPI,但5-HT2A受体拮抗剂M100907没有这种作用。此外,TCB-2局部输注到伏隔核和腹侧苍白球破坏的PPI,而在内侧前额叶皮层进行同样的操作,腹侧海马,腹侧被盖区没有破坏PPI。总之,腹侧苍白球和伏隔核中5-HT2A受体的激动作用可以破坏PPI。腹侧苍白球和伏隔核是负责5-羟色胺调节PPI的关键大脑区域。这些发现有助于广泛探索5-HT2A受体活性对PPI的调节作用的分子和神经机制。特别是由5-HT2A受体活性调节的神经回路。