Reappraisal of spontaneous stereotypy in the deer mouse as an animal model of obsessive-compulsive disorder (OCD): response to escitalopram treatment and basal serotonin transporter (SERT) density

Abstract

Obsessive-compulsive disorder (OCD) is characterized by recurrent thoughts and repetitive motor actions. Hyposerotonergic signalling in the cortico-striatal circuitry is believed to be central to the pathology of OCD, while many patients only respond to chronic treatment with high dose selective serotonin (5HT) reuptake inhibitors (SSRIs). Confined deer mice spontaneously develop two forms of stereotypy, namely vertical jumping and pattern running. The purpose of this investigation was to reappraise these behaviours and strengthen the validity of deer mouse stereotypy as an animal model of OCD within a framework of three study questions: (1) can the time spent executing stereotypical behaviours be employed as a measure of extent of stereotypy, (2) does deer mouse stereotypy only respond to chronic, but not sub-chronic treatment with a high-dose SSRI, and (3) is deer mouse stereotypy associated with altered cortico-striatal 5HT transporter (SERT) binding? The current study demonstrates that treatment naïve high stereotypical (HS) deer mice spend significantly more time executing stereotypical behaviours while significantly less time is spent indulging in stereotypy following chronic, but not sub-chronic, treatment with escitalopram. Furthermore, HS deer mice present with a significant decrease in striatal SERT density compared to non-stereotypical (NS) controls. Building on previous validation studies, we conclude that deer mouse stereotypy is a valid naturalistic animal model of OCD with robust face, construct and predictive validity.

Keywords: 5HT; CR; DA; Deer mouse; Escitalopram; Frontal cortex-striatum; HS; OC; OCD; Obsessive-compulsive disorder (OCD); SERT; SSRI; Serotonin transporter (SERT); Stereotypy; VBI; [NS/LS]; cage revolutions (indication of pattern running activity); dopamine; high-stereotypical; non- and low-stereotypical; obsessive-compulsive; obsessive-compulsive disorder; selective serotonin reuptake inhibitor; serotonin; serotonin transporter; vertical beam interruptions (indication of jumping activity).