Oxytocin Prevents the Development of 3-NP-Induced Anxiety and Depression in Male and Female Rats: Possible Interaction o
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ORIGINAL RESEARCH
Oxytocin Prevents the Development of 3‑NP‑Induced Anxiety and Depression in Male and Female Rats: Possible Interaction of OXTR and mGluR2 Fariba Khodagholi1 · Ali Maleki1 · Fereshteh Motamedi1 · Maryam Alsadat Mousavi2 · Shahrbanoo Rafiei2 · Mehdi Moslemi2 Received: 24 July 2020 / Accepted: 7 November 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Huntington disease (HD) is a progressive neurological disorder with dominant motor symptoms. It also has psychiatric manifestations, like anxiety and depression, that can emerge themselves before motor symptoms and impose a major burden on patients. Oxytocin (OXT) is a newly emerged treatment for disorders like autism and schizophrenia and recently is using to alleviate depression and anxiety. In the current study, we investigated the behavioral and molecular effects of OXT on the development of anxiety and depression in 3-nitropropionic acid (3-NP)-induced model of HD. Anxiety- and depression-like behaviors as well as the levels of oxytocin receptor (OXTR), metabotropic glutamate receptor (mGluR) 2, mGluR5, and glutathione (GSH) were measured in striatum, hippocampus, prefrontal cortex, and amygdala. Also, we questioned if sex had any modulatory effect. We found that 3-NP increased anxiety and depression compared to controls. It also reduced the levels of OXTR and mGluR2, increased mGluR5, and reduced GSH in studied brain regions. Pretreatment with OXT before the injection of 3-NP ameliorated anxiety and depression. Additionally, it protected the brain from developing low levels of OXTR, mGluR2, and GSH and high levels of mGluR5 in studied regions. The protective effects of OXT were similar between male and female animals. These data suggest that OXTR, mGluR2, mGluR5, and GSH may contribute to psychiatric manifestations of HD. In addition, pretreatment with OXT could prevent the mood changes in male and female rats. Keywords Oxytocin · 3-NP · Huntington disease · Depression · Anxiety
Introduction Huntington disease (HD) is a neurodegenerative disorder affecting brain structures like striatum and leads to a combination of motor, behavioral, and cognitive disorders. Patients with HD display progressive motor disability with involuntary abnormal movements manifesting as chorea movements in early stages which later is followed by akinesia and sometimes dystonia (Roos 2010). However, the non-motor symptoms of HD including depression and anxiety could be more devastating than movement disorders and typically * Mehdi Moslemi [email protected] 1
Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Neurobiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
2
precede the onset of motor abnormalities (Petersen and Gabery 2012). They affect approximately 50% of patients with HD (Craufurd et al. 2001) and may appear due to hypothalamic and limbic system alterations as the key structures regulating psychiatric features (Kotliarova et al. 200
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