Effects of desformylflustrabromine on compulsive-like and social behaviors in mouse models of OCD and autism

Abstract

Obsessive-Compulsive Disorder (OCD) and autism spectrum disorders (ASD) share a number of similar deficits, including altered cholinergic activity in the central nervous system (CNS), manifestation of repetitive, restricted, and compulsive-like patterns of behavior, and frequent co-morbid presentation. Desformylflustrabromine is a novel positive allosteric modulator of α4β2 nicotinic acetylcholine receptors, which has recently been shown to be able to reduce compulsive-like behavior in a non-induced mouse model of OCD. In this study, I attempted to replicate the compulsive-like behavior-reducing effects of desformylflustrabromine in the mouse model of OCD, as well as expose the model to a novel assessment; social behavior, as measured by the 3-Chamber Social test. Furthermore, I altered the model with prenatal exposure to valproic acid to induce an ASD-like construct. This ASD animal model has been used extensively to study the social deficits and neurochemistry of ASD, although limited data exists on co-morbid models. By exposing the OCD model to valproic acid, I attempted to establish two additional models; a comorbid OCD / ASD model in the compulsive-like high-activity (HA) strain and an ASD model in the non-compulsive-like low-activity (LA) strain. All mouse models and controls participated in a battery of behavioral tests quantifying compulsive-, anxiety-, and depression-like behaviors, as well as the 3-chamber social test to quantify social preference behaviors. The ASD model was not strongly established, and the desformylflustrabromine appeared to be inactive in all strains and models. I assessed potential reasons for the failure to establish a robust ASD construct in the OCD mouse model, and the failure of desformylflustrabromine to have any significant effect, in contrast with previous research using the drug in the OCD mouse model.