5-HT1A-receptor agonist modified amygdala activity and amygdala-Associated social behavior in a valproate-induced rat autism model

Chao Chuan Wang, Hui Ching Lin, Yun Han Chan, Po Wu Gean, Yen Kung Yang, Po See Chen

研究成果: Article

21 引文 斯高帕斯(Scopus)

摘要

Accumulating evidence suggests that dysfunction of the amygdala is related to abnormal fear processing, anxiety, and social behaviors noted in autistic spectrum disorders (ASDs). In addition, studies have shown that disrupted brain serotonin homeostasis is linked to ASD. With a valproate (VPA)-induced rat ASD model, we investigated the possible role of amygdala serotonin homeostasis in autistic phenotypes and further explored the underlying mechanism. We first discovered that the distribution of tryptophan hydroxylase immunoreactivity in the caudal raphe system was modulated on postnatal day (PD) 28 of the VPA-exposed offspring. Then, we found a significantly higher serotonin transporter availability in the amygdala of the VPA-exposed offspring on PD 56 by using single photon emission computed tomography and computed tomography co-registration following injection of 123I-labeled 2-((2-(dimethylamino)methyl)phenyl)thio)-5-iodophenylamine(123I[ADAM] ). Furthermore, treatment with 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a 5-HT1A receptor agonist, increased social interaction and improved fear memory extinction in the VPA-exposed offspring. 8-OH-DPAT treatment also reversed the characteristics of miniature excitatory post-synaptic currents as well as paired pulse facilitation observed in lateral amygdala slices. These results provided further evidence to support the role of the amygdala in characteristic behavioral changes in the rat ASD model. The serotonergic projections that modulate the amygdala function might play a certain role in the development and treatment of behavioral symptoms exhibited in individuals with ASD.

原文English
頁(從 - 到)2027-2039
頁數13
期刊International Journal of Neuropsychopharmacology
16
發行號9
DOIs
出版狀態Published - 2013 十月 1

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

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