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OSR Journal of Student Research

Article Title

The 5-HT6 receptor BGC 20-761 attenuates repetitive behaviors in the BTBR mouse model of autism spectrum disorder

Abstract

Autism spectrum disorder (ASD) is defined by two core symptoms of restricted, repetitive behaviors (RRBs) and social-communication deficits. The BTBR T+ tf/J (BTBR) mouse, like ASD individuals, exhibits increased stereotypic motor behaviors and an impaired behavioral flexibility. In the search of new therapeutic pharmacological targets for these repetitive behaviors, the 5-hydroxytrptamine 6 (5-HT6) receptor is of interest because blockade has shown to be pro-cognitive while showing promise as a treatment in the attenuation of behavioral inflexibility. The current study aimed to better understand how 5-HT6 receptor blockade may attenuate repetitive grooming and behavioral inflexibility in BTBR mice. Mice were treated with the 5-HT6 receptor antagonist BGC 20-761 then tested for repetitive grooming behavior and performance on the radial 8-arm memory task, a test of behavioral flexibility. We predicted that the 5-HT6 receptor antagonist would attenuate both repetitive grooming and spatial 8-arm memory performance. Results indicate that vehicle treated BTBR mice expressed elevated levels of grooming compared to vehicle treated C57BL/6J mice. BTBR mice treated with the 5-HT6 receptor antagonist BGC 20-761 groomed less compared to vehicle treated BTBR mice. Initial data suggests that BGC 20-761 treatment attenuates behavioral inflexibility in BTBR mice compared to vehicle treated BTBR mice. Together, BGC 20-761 treatment reduced repetitive grooming behavior and behavior inflexibility in the BTBR mouse model of ASD. Therefore, 5-HT6 receptor blockade is a novel therapeutic aimed at attenuating RRBs in ASD.

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