Reporting of ethical aspects in validation studies conducted in Peru.

Obsessive-compulsive disorder (OCD) is a chronic, debilitating disorder affecting 1–3% of the population. It is characterized by recurring distressing thoughts (obsessions) and ritualized actions (i.e. compulsions) that are often performed to avoid the perceived harmful outcomes of obsessions and obtain relief from obsession-related distress []. The link between obsessions, compulsions, and avoidance is further highlighted by studies showing that impairments in threat processing and avoidance are associated with compulsion severity and poorer treatment outcomes in OCD [–]. Additionally, OCD patients exhibit biases to attend to and learn to avoid negative stimuli [, ], habitually avoid devalued threats [], have devaluation impairments on a rule-based avoidance task with longer illness duration [], and inappropriately perform avoidant behaviors in response to safety cues []. Together, these studies suggest that persistent active avoidance could contribute to the development and severity of OCD, but little is known about the mechanisms underlying this dysregulation. Active avoidance is a defensive behavioral response in which an action is performed to prevent exposure to a threat. Common preclinical models include shuttle avoidance, in which rodents are conditioned to run across a chamber to avoid shocks administered on one half of a shuttlebox, and platform avoidance, in which rodents can avoid shocks by stepping onto a platform to prevent contact with a grid floor delivering a foot shock. The platform-mediated avoidance task (PMA) specifically involves rodents choosing between lever pressing for rewards or making an avoidance response by mounting a platform during a cue that predicts a foot shock. This design allows modeling of conflict-based active avoidance, a critical feature of maladaptive avoidant behaviors [, ]. In addition, extinction of platform avoidance can be performed using exposure with response prevention (ERP) [] to model the gold-standard behavioral therapy for OCD [], which involves patients refraining from completing rituals in the presence of obsession-related stimuli, making this a powerful translational model for understanding how avoidant behaviors are extinguished or persist following ERP []. Studies in rodents have identified circuits involved in PMA conditioning and extinction whose homologues are also implicated in neuroimaging studies of avoidance in OCD patients, including medial prefrontal cortex and striatal regions relevant to threat appraisal and motivated behaviors altered in OCD [–]. Testing of OCD-relevant transgenic mice on this task may therefore provide important opportunities for identifying disease relevant mechanisms. knockout mice (KOs) - a transgenic line with deletion of the postsynaptic scaffolding protein Sapap3 - are a common model for OCD-related behaviors, exhibiting compulsive grooming [–], elevated anxiety [, ], and deficits in behavioral flexibility [, –] relevant to symptoms observed in clinical populations [, ]. Recent studies also demonstrate enhanced fear conditioning and impaired fear extinction in KOs [[, ], (Ahmari lab, unpublished observations)], suggesting heightened sensitivity to negative stimuli and threat appraisal. Therefore, identifying behavioral and neurobiological changes associated with avoidance acquisition, extinction, or conflict-based reward seeking in -KOs using the PMA task could provide valuable information for understanding alterations in avoidance behavior and associated symptoms in OCD. While one study has investigated -KO performance in PMA conditioning and extinction [], no studies have examined how KOs extinguish or persist in platform avoidance following ERP. Furthermore, the previous study from St. Laurent et al. [] did not investigate changes in reward-seeking under motivational conflict across platform avoidance conditioning and extinction. Potential differences in reward-seeking vs avoidance conflict in -KOs, and mechanisms underlying these decision-making processes, remain unknown.