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Role of the Dorsal Striatum and 5-HT2A receptor in a mouse model of autism
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
2015 (English)Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
Abstract [en]

BACKGROUND: Some cases of autism spectrum disorder (ASD) are associated with genetic causes. A micro deletion on the human chromosome 16p11.2 is the most common. A mouse model with this deletion demonstrates functional abnormalities in the basal ganglia (BG), mainly the striatum. 5-HT2A receptors are also present in the striatum and may provide substrate for modulating the BG circuitry that possibly has a crucial role in ASD. AIM: To examine neuron activity in the striatum, qualitatively observe the distribution of the 5-HT2A receptor in the striatum and pharmacologically investigate serotonin 5-HT2A involvement in the behavioral abnormalities found in 16p11.2 deletion mice. METHODS: Expression of the gene product of c-fos was measured using immunohistochemistry to provide a measure of neural activity. Autoradiography was used to describe the distribution of the 5-HT2A receptors in the striatum. The effect of risperidone and M100907 on 16p11.2 deletion mice was assayed using the forced swim test. RESULTS: A significant increase in c-fos expression in the dorsal striatum in mutant mice was observed. Both normal and deletion mice exhibited receptor binding to 5-HT2A in the striatum. A significant decrease in mobility in the forced swim test in both mutant and wild type mice was observed only when risperidone was administrated compared to controls and M100907. CONCLUSION: Elevated c-fos expression in the dorsal striatum indicates altered activity in dorsal striatum in this ASD mouse model. 5-HT2A receptor binding in the striatum is qualitatively similar in both genotypes. Risperidone had a greater effect than M100907 in normalizing behavioral response in the swim, yet further dose-response and behavioral studies has to be done for more accurate determinations about the involvement of 5-HT2A as a possible pharmacological target for treatment in autism.

Place, publisher, year, edition, pages
2015.
Keyword [en]
Autism, 5-HT2A, dorsal striatum, c-fos
National Category
Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-242728OAI: oai:DiVA.org:uu-242728DiVA: diva2:784825
External cooperation
Boston Children's Hospital / Harvard Medical School
Subject / course
Pharmaceutical Biosciences
Educational program
Master of Science Programme in Pharmacy
Supervisors
Examiners
Available from: 2015-02-02 Created: 2015-01-30 Last updated: 2015-02-02Bibliographically approved

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CiteExportLink to record
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