Postpartum Lactation-Mediated Behavioral Outcomes and Drug Responses in a Spontaneous Mouse Model of Obsessive–Compulsive Disorder

Abstract

Using a spontaneous mouse model of obsessive-compulsive disorder (OCD), the current study evaluated the influence of postpartum lactation on the expression of compulsive-like behaviors, SSRI effectiveness, and the putative role of oxytocin and dopamine in mediating these lactation specific behavioral outcomes. Compulsive-like lactating mice were less compulsive-like in nest building and marble burying and showed enhanced responsiveness to fluoxetine (50 mg/kg) in comparison to compulsive-like nonlactating and nulliparous females. Lactating mice exhibited more anxiety-like behavior in the open field test compared to the nulliparous females, while chronic fluoxetine reduced anxiety-like behaviors. Blocking the oxytocin receptor with L368-899 (5 mg/kg) in the lactating mice exacerbated the compulsive-like and depression-like behaviors. The dopamine D2 receptor (D2R) agonist bromocriptine (10 mg/kg) suppressed marble burying, nest building, and central entries in the open field, but because it also suppressed overall locomotion in the open field, activation of the D2R receptor may have inhibited overall activity nonspecifically. Lactation- and fluoxetine-mediated behavioral outcomes in compulsive-like mice, therefore, appear to be partly regulated by oxytocinergic mechanisms. Serotonin immunoreactivity and serum levels were higher in lactating compulsive-like mice compared to nonlactating and nulliparous compulsive-like females. Together, these results suggest behavioral modulation, serotonergic alterations, and changes in SSRI effectiveness during lactation in compulsive-like mice. This warrants further investigation of postpartum events in OCD patients.

Oxytocin receptor knockout prairie voles generated by CRISPR/Cas9 editing show reduced preference for social novelty and exaggerated repetitive behaviors

“…Previous work showed that mice infected with lentivirus expressing Oxtr in nucleus accumbens, and intracerebroventricularly injected with OXT, reduced marble burying behaviors (Bahi et al, 2016;Sanathara et al, 2018). Additionally, lactating female mice intraperitoneally injected with OXTR antagonist buried a higher number of marbles than those injected with vehicle (Mitra et al, 2017). Although these results indicated that OXTR signaling modulates repetitive behavior in male and female mice, to our knowledge, there have been no study to analyze repetitive behavior in MBT with Oxtr gene modified mice, or prairie voles.…”

Bidirectional Behavioral Selection in Mice: A Novel Pre-clinical Approach to Examining Compulsivity

“…Spontaneous animal models use the concept of innately occurring stereotypic behaviors, motor behaviors, or adjunctive behaviors that are induced through behavioral manipulations (146)(147)(148). Animal behaviors that are suggested to be relevant to OCD (149,150) include excessive grooming (151,152), acral lick (153)(154)(155) and stereotopies (156,157) in several species such as dogs, psychogenic alopecia in cats (158)(159)(160), repetitive pacing in captive wild animals (161)(162)(163), feather picking in birds (151,(164)(165)(166), repetitive behaviors, such as running, flipping and jumping in deer mice (167,168) and cribbing in horses (169)(170)(171)(172)(173), spontaneous alteration (174), compulsive checking by mice and rats (174), marble burying behavior (digging) in mice (140)(141)(142)(143)(144)(145)175) and rats (149), signal attenuation in rats (176,177), and nest-building behavior (140)(141)…”

“…While prior reviews have discussed extensively the existing animal models of OCD, we only describe these animal models briefly here and focus particularly on the spontaneous compulsive-like nest-building phenotype (140)(141)(142)(143)(144)(145) and argue in favor of this model as suitable for understanding behavioral plasticity underlying expression of compulsivity typically reported in OCD and OCRD.…”

Complex interaction of dietary fat and Alaskan bog blueberry supplementation influences manganese mediated neurotoxicity and behavioral impairments

“…The open field apparatus consisted of an arena (40 cm × 40 cm × 30 cm) with opaque plexiglass walls. Testing was conducted for a 3-min duration Mitra, Mucha, Owen, & Bult-Ito, 2017). Animals were individually placed in the center of the field and allowed to explore the arena.…”