Ovarian Sex Hormones Modulate Compulsive, Affective and Cognitive Functions in A Non-Induced Mouse Model of Obsessive-Compulsive Disorder

Abstract

There is currently a lack of understanding of how surgical menopause can influence obsessions, compulsions and associated affective and cognitive functions in female obsessive-compulsive disorder (OCD) patients. Early menopause in women due to surgical removal of ovaries not only causes dramatic hormonal changes, but also may induce affective and cognitive disorders. Here, we tested if surgical removal of ovaries (ovariectomy, OVX), which mimics surgical menopause in humans, would result in exacerbation of compulsive, affective and cognitive behaviors in mice strains that exhibit a spontaneous compulsive-like phenotype. Female mice from compulsive-like BIG, non-compulsive SMALL and randomly-bred Control strains were subjected to OVX or sham-surgery. After 7 days animals were tested for nest building and marble burying to measure compulsive-like behavior. The elevated plus maze and open field tests measured anxiety-like behaviors, while memory was assessed by the novel object recognition. Acute OVX resulted in exacerbation of compulsive-like and anxiety-like behaviors in compulsive-like BIG mice. No significant effects of OVX were observed for the non-compulsive SMALL and Control strains. Object recognition memory was impaired in compulsive-like BIG female mice compared to the Control mice, without an effect of OVX on the BIG mice. We also tested whether 17 β-estradiol (E2) or progesterone (P4) could reverse the effects of OVX. E2, but not P4, attenuated the compulsive-like behaviors in compulsive-like BIG OVX female mice. The actions of the sex steroids on anxiety-like behaviors in OVX females were strain and behavioral test dependent. Altogether, our results indicate that already existing compulsions can be worsened during acute ovarian deprivation concomitant with exacerbation of affective behaviors and responses to hormonal intervention in OVX female mice can be influenced by genetic background.

Melanin concentrating hormone modulates oxytocin-mediated marble burying

“…The data also show that OT-MCH relationship did not extend to exploratory or anxiety related behaviors as assayed through open-field, light-dark box, and elevated plus maze assays. This data support previous reports demonstrating that marble-burying does not reflect an anxiety response (Thomas et al, 2009; Greene-Schloesser et al, 2011; Angoa-Perez et al, 2013; Aguilar-Valles et al, 2015; Mitra et al, 2016a, 2016b, 2017). As previously reported, we also found that OT infusions increased genital grooming but MCH infusions did not (Amico et al, 2004).…”

Identification of hepatic fibroblast growth factor 21 as a mediator in 17β‐estradiol‐induced white adipose tissue browning

“…The abdominal wall and the skin were then sutured. After a 2-wk recovery, mice received a single subcutaneous injection of vehicle (corn oil, C8267; MilliporeSigma, Billerica, MA, USA) or E2 (E8875; MilliporeSigma) at a dosage of 0.5 mg/kg, which was able to achieve 5 times greater circulation of E2 than that at proestrus (27).…”

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

“…Time spent exploring the familiar and novel objects were recorded. The preference of one object over another was assessed through the recognition index (RI), which was determined by the time spent on the novel object relative to the time spent on both novel and familiar objects: [RI = TN/(TN+TF)] where TN is time spent on the novel object and TF is time spent on the familiar object (Mitra, Bastos, Bates, Pereira, & Bult-Ito, 2016). Objects and exploration arena were cleaned with a dilute chlorhexidine solution after each animal.…”