5HT2A Receptor Antagonist Treatment for Repetitive Behaviors and Restricted Interests in BTBR Mice
thesisposted on 2015-10-21, 00:00 authored by Dionisio A. Amodeo
Individuals with autism spectrum disorder (ASD) commonly exhibit an “insistence on sameness” which is characterized by a compulsive adherence to a thought pattern or stereotyped behavior. Insistence on sameness in ASD can result in behavioral flexibility deficits when a situation requires a shift in thought patterns or actions. To date, there lacks effective treatments to alleviate insistence on sameness features, which is in part due to the limited knowledge about the underlying neuropathophysiology contributing to behavioral inflexibility and stereotyped behavior. This project investigated whether pharmacologically targeting 5HT2A receptors in an idiopathic model of ASD, the BTBR mouse, affects the expression of a phenotype that is related to RRBs in ASD. The findings suggest that altered 5HT2A receptor signaling in BTBR mice may contribute to behavioral flexibility deficits and elevated grooming which can be attenuated by systemic treatment with a 5HT2A receptor antagonist. A behavioral flexibility deficit observed in BTBR mice may result, in part, from increased 5HT2A receptor signaling in the dorsomedial striatum. In contrast, 5HT2A receptor signaling in the orbitofrontal cortex may be normal in BTBR mice, but when 5HT2A receptor blockade of this region leads to perseveration of both cognitive and stereotyped behaviors. Overall, these findings suggest that 5HT2A receptor antagonist treatment may be effective in ameliorating RRBs in ASD, in part, by correcting altered 5HT2A receptor signaling in the striatum.