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.
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This work was supported by Shahid Beheshti University of Medical Sciences Research Funds (Grant No.15693-1).
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This work was supported by Shahid Beheshti University of Medical Sciences Research Funds (Grant No.15693-1).
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[Fariba Khodagholi], [Ali Maleki], [Fereshteh Motamedi], and [Mehdi Moslemi] participated in the study design.[Shahrbanoo Rafiei] and [Mehdi Moslemi] contributed in data analysis.[Fariba Khodagholi], [Ali Maleki], [Maryamalsadat Mousavi], and [Mehdi Moslemi] contributed in data interpretation and writing the manuscript.[Fariba Khodagholi] and [Fereshteh Motamedi] contributed in editing the manuscript. All authors read and approved the final manuscript.
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Experiments were conducted according the Care and Use of Laboratory Animals (NIH publication, 85-23, revised 1996) guidelines and approved by the Shahid Beheshti University of Medical Sciences Ethics Committee. Written ratification for the study was received from the Neuroscience Research Center Ethics Board (IR.SBMU.PHNS.REC.1397.016).
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Khodagholi, F., Maleki, A., Motamedi, F. et al. Oxytocin Prevents the Development of 3-NP-Induced Anxiety and Depression in Male and Female Rats: Possible Interaction of OXTR and mGluR2. Cell Mol Neurobiol 42, 1105–1123 (2022). https://doi.org/10.1007/s10571-020-01003-0
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DOI: https://doi.org/10.1007/s10571-020-01003-0