Acquisition and extinction of active avoidance compulsive-like behavior in mice

Abstract

Approximately 90% of adults have ever experienced obsessions, yet less than 3% of them develop OCD. It is hypothesized that excessive fear of negative events contributes to OCD onset and development, which is related to the individual differences in psychopathology and neurophysiology associated with OCD among those who experience obsessions. To explore the hypothesis, this study examined if a fear-inducing aversive footshock could induce compulsive-like lever-pressing behavior in mice, the effects of extinction treatments on the compulsive-like behavior, and how the expression of tryptophan hydroxylase 2 (TPH2) in the amygdala would be regulated. This study successfully established a novel active avoidance OCD model in mice (model mice), manifesting compulsive-like lever-pressing with a smaller range of exploring in response to fear-inducing footshock. The compulsive-like behavior could be alleviated. The TPH2 in the left amygdala was down-regulated in model mice but up-regulated after food treatment and fluoxetine treatment. Food was the most effective treatment for reducing compulsive-like behavior and up-regulating the TPH2 levels in the left amygdala, followed by fluoxetine, sham, and sound. Our findings elucidate the fundamental processes of the acquisition and extinction of an active avoidance compulsive-like behavior in mice and provide insight into potential interventions to improve the prognosis of the compulsive-like behavior. This study provides evidence that the acquisition and extinction of active avoidance compulsive-like behavior in mice is associated with neuroplasticity relevant to protein regulation affected by brain-environment interactions.