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


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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