Key Laboratory of Cognition and Personality (Southwest University), Ministry of Education, Chongqing, China; Faculty of Psychology, Southwest University, Chongqing, China.
Key Laboratory of Cognition and Personality (Southwest University), Ministry of Education, Chongqing, China; Faculty of Psychology, Southwest University, Chongqing, China.
Prog Neuropsychopharmacol Biol Psychiatry. 2022 Mar 8;113:110441. doi: 10.1016/j.pnpbp.2021.110441. Epub 2021 Sep 21.
Prepulse inhibition (PPI) is disrupted in many neuropsychiatric diseases. Molecules such as 5-HT receptor agonists alleviate PPI deficits in rodents; however, the precise mechanisms and critical regions of the brain responsible for the reversal effect of these agonists remain inconclusive. The present study aimed to investigate the areas of the brain critical for the reversal effect of 5-HT receptor agonists on PPI deficits in mice. The results showed that systemic administration of the 5-HT receptor agonist MK212 did not affect normal PPI behavior, but reversed the PPI deficits induced by the N-methyl d-aspartate receptor antagonist MK801 in mice. In addition, the 5-HT receptor antagonist SB242084 had no effect on PPI behavior despite MK801 treatment. Moreover, local infusion of MK212 into the medial prefrontal cortex and ventral hippocampus, excluding the nucleus accumbens or ventral tegmental area, rescued the PPI deficits induced by MK801. These data suggest that the medial prefrontal cortex and ventral hippocampus are critical brain areas responsible for the reversal of 5-HT agonists on PPI deficits. The results will contribute to our current knowledge on the molecular and neural mechanisms underlying the antipsychotic effects of 5-HT receptor agonists, especially the neural circuits modulated by 5-HT receptor activity.
前脉冲抑制（PPI）在许多神经精神疾病中受到破坏。 5-HT 受体激动剂等分子可减轻啮齿动物的 PPI 缺陷； 然而，这些激动剂逆转作用的确切机制和关键脑区仍不清楚。 本研究旨在探讨大脑中对 5-HT 受体激动剂逆转 PPI 缺陷的关键区域。 结果表明，全身给予 5-HT 受体激动剂 MK212 不会影响正常的 PPI 行为，但可逆转 N-甲基-D-天冬氨酸受体拮抗剂 MK801 诱导的 PPI 缺陷。 此外，5-HT 受体拮抗剂 SB242084 尽管给予 MK801 也没有影响 PPI 行为。 此外，MK212 局部输注到前额叶皮质和海马腹侧部，而不包括伏隔核或腹侧被盖区，可挽救 MK801 诱导的 PPI 缺陷。 这些数据表明，前额叶皮质和海马腹侧部是负责 5-HT 激动剂逆转 PPI 缺陷的关键脑区。 这些结果将有助于我们目前对 5-HT 受体激动剂抗精神病作用的分子和神经机制的认识，特别是 5-HT 受体活性调节的神经回路。
