Involvement of D1 and D2 dopamine receptors in the antidepressant-like effects of selegiline in maternal separation model of mouse

Amiri, Shayan; Amini-Khoei, Hossein; Mohammadi-Asl, Ali; Alijanpour, Sakineh; Haj‐Mirzaian, Arya; Rahimi-Balaei, Maryam; Razmi, Ali; Olson, Carl O.; Rastegar, Mojgan; Mehdizadeh, Mehdi; Zarrindast, Mohammad Reza

doi:10.1016/j.physbeh.2016.04.052

Cited by 51 publications

(27 citation statements)

References 68 publications

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“…Increased immobility time in the FST was considered behavioral despair, i.e. a symptom of human depression (Amiri et al, 2016). One-way ANOVA results suggested a significant difference in the FST scores [F (3, 27) =38.462, P<0.001].…”

Section: Resultsmentioning

confidence: 99%

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Therapeutic Effect of Exercise on Anxiety and Bowel Oxidative Stress in the Maternal Separation Animal Model

Khorjahani

Peeri

Azarbayjani

2019

Basic Clin. Neurosci. J.

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According to evidence, Early-Life Stress (ELS), mood disorders, and medical comorbidities, i.e. Irritable Bowel Syndrome (IBS), are correlated; however, the direct contribution of ELS to IBS manifestations is less understood. The current study aimed at evaluating the effect of voluntary exercise on the mitochondrial dysfunction of the bowel fibroblasts, following the confirmation of anxiety behavior. Methods: In this study, Postnatal Day (PND) rats underwent Maternal Separation (MS), as a valid animal model of the brain-gut axis dysfunction, in the days 2-14; three hours daily. On day 21, the study animals were divided into 4 groups, as follows: control, Running Wheel (RW) exercise, MS, and MS+RW groups. The study groups were housed in separate cages (4 rats per cage) until the onset of intervention. On day 60, the elevated plus-maze was used to assess anxiety-like behaviors; the level of oxidative stress biomarkers, i.e. Reactive Oxygen Species (ROS), Glutathione (GSH) , as well as Adenosine Triphosphate (ATP) was measured to determine the gut mitochondrial function. Results: Findings revealed that ELS affected the gut energy metabolism in the studied rats; the negative effects of MS on anxiety and the gut mitochondrial dysfunction decreased via RW exercise during adolescence. Conclusion: Overall, anxiety behaviors and ROS production, leading to increased GSH and ATP levels, improved after RW exercise; this significantly impacts the function of colon secretory mitochondria. According to the positive effects of RW exercise on mitochondrial dysfunction in an ELS animal model, a potential relationship was found between the brain and gut in the study rats.

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Section: Resultsmentioning

confidence: 99%

“…Thus, 5 µL of 10 µM DCFH-DA was added to the supernatant, composed of respiratory buffer (Sonei et al, 2017). The amount of DCF, final fluorescent product, was determined at the excitation-emission wavelengths of 485 and 525 nm, respectively (Amiri et al, 2016;Sonei et al, 2017).…”

Section: Methodsmentioning

confidence: 99%

Therapeutic Effect of Exercise on Anxiety and Bowel Oxidative Stress in the Maternal Separation Animal Model

Khorjahani

Peeri

Azarbayjani

2019

Basic Clin. Neurosci. J.

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“…Moreover, 10 mg/kg selegiline normalized FST-induced decreases in striatal 5-HT and cortical NE content after the FST in CD157 KO mice. The antidepressant effects of selegiline in the FST may be mediated by the activation of D1 receptors (Shimazu et al, 2005; Amiri et al, 2016). Our data therefore suggest that the antidepressant effect of selegiline is attributable at least partially to the improvement of serotonergic, noradrenergic and dopaminergic dysfunction in CD157 KO mice.…”

Section: Discussionmentioning

confidence: 99%

“…DA induces motivation, reward and hedonic states, and plays an important role in neuropsychiatric disorders such as depression. Selegiline was reported to have antidepressant effects mediated by the activation of D1 and D2 receptors in normal and depressed mice (Shimazu et al, 2005; Amiri et al, 2016). Moreover, several studies have shown that selegiline enhances the expression of brain-derived neurotrophic factor in cultured murine astrocytes and in the anterior cingulate cortex of mice (Mizuta et al, 2000; Gyárfás et al, 2010), and prevents dopaminergic neurons from degeneration (Zhu et al, 2008; Youdim, 2013; Kong et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Selegiline Ameliorates Depression-Like Behavior in Mice Lacking the CD157/BST1 Gene, a Risk Factor for Parkinson’s Disease

Kasai

Yoshihara

Lopatina

et al. 2017

Front. Behav. Neurosci.

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Parkinson’s disease (PD), a neurodegenerative disorder, is accompanied by various non-motor symptoms including depression and anxiety, which may precede the onset of motor symptoms. Selegiline is an irreversible monoamine oxidase-B (MAO-B) inhibitor, and is widely used in the treatment of PD and major depression. However, there are few reports about the effects of selegiline on non-motor symptoms in PD. The aim of this study was to explore the antidepressant and anxiolytic effects of selegiline, using CD157/BST1 knockout (CD157 KO) mouse, a PD-related genetic model displaying depression and anxiety, compared with other antiparkinsonian drugs and an antidepressant, and was to investigate the effects of selegiline on biochemical parameters in emotion-related brain regions. A single administration of selegiline (1–10 mg/kg) dose-dependently reduced immobility time in the forced swimming test (FST) in CD157 KO mice, but not C57BL/6N wild-type (WT) mice. At 10 mg/kg, but not 3 mg/kg, selegiline significantly increased climbing time in CD157 KO mice. A single administration of the antiparkinsonian drugs pramipexole (a dopamine (DA) D2/D3 receptor agonist) or rasagiline (another MAO-B inhibitor), and repeated injections of a noradrenergic and specific serotonergic antidepressant (NaSSA), mirtazapine, also decreased immobility time, but did not increase climbing time, in CD157 KO mice. The antidepressant-like effects of 10 mg/kg selegiline were comparable to those of 10 mg/kg rasagiline, and tended to be stronger than those of 1 mg/kg rasagiline. After the FST, CD157 KO mice showed decreases in striatal and hippocampal serotonin (5-HT) content, cortical norepinephrine (NE) content, and plasma corticosterone concentration. A single administration of selegiline at 10 mg/kg returned striatal 5-HT, cortical NE, and plasma corticosterone levels to those observed in WT mice. In the open field test (OFT), repeated administration of mirtazapine had anxiolytic effects, and selegiline nonsignificantly ameliorated anxiety-like behaviors in CD157 KO mice. In the social interaction and preference tests, repeated mirtazapine ameliorated the high anxiety and low sociability of CD157 KO mice, whereas selegiline did not. These results indicate that selegiline has antidepressant and mild anxiolytic effects in CD157 KO mice, and suggest that it is an effective antiparkinsonian drug for depressive and anxiety symptoms in PD patients with a CD157 single nucleotide polymorphism (SNP).

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“…When pups were born, they were subjected to the NMS paradigm at PND 1. The NMS paradigm, similar to previous protocols ( Amini-Khoei et al, 2015 ; Amiri et al, 2016 ), was used with slight modifications. The male offsprings were separated from their mothers for 4 h daily during PND 9–15 for a short-term separation or PND 1–20 for a long-term separation, beginning at 10:00 a.m., and were returned to their mothers after the 4-h separation period.…”

Section: Methodsmentioning

confidence: 99%

Involvement of Oxytocin Receptor/Erk/MAPK Signaling in the mPFC in Early Life Stress-Induced Autistic-Like Behaviors

Wei

et al. 2020

Front. Cell Dev. Biol.

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The neonatal or infant period is a critical stage for the development of brain neuroplasticity. Early life stresses in the neonatal period, including neonatal maternal separation (NMS), have adverse effects on an increased risk of psychiatric disorders in juveniles and adults. However, the underlying molecular mechanisms are not largely understood. Here, we found that juvenile rats subjected to 4 h daily NMS during postnatal days 1 to 20 exhibited autistic-like behavioral deficits without impairments in learning and memory functions. Molecular mechanism studies showed that oxytocin receptor (OXTR) in the medial prefrontal cortex of NMS rats was evidently downregulated when compared with control pups, especially in neurons. Erk/MAPK signaling, the downstream coupling signaling of OTXR, was also inhibited in NMS juvenile rats. Treatment with oxytocin could relieve NMS-induced social deficit behaviors and activated phosphorylation of Erk/MAPK signaling. Furthermore, medication with the inhibitor of H3K4 demethylase alleviated the abnormal behaviors in NMS rats and increased the expression of OXTR in the medial prefrontal cortex, which showed an epigenetic mechanism underlying social deficits induced by NMS. Taken together, these findings identified a molecular mechanism by which disruptions of mother–infant interactions influenced later displays of typical social behaviors and suggested the potential for NMS-driven epigenetic tuning of OXTR expression.

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Involvement of D1 and D2 dopamine receptors in the antidepressant-like effects of selegiline in maternal separation model of mouse

Cited by 51 publications

References 68 publications

Therapeutic Effect of Exercise on Anxiety and Bowel Oxidative Stress in the Maternal Separation Animal Model

Therapeutic Effect of Exercise on Anxiety and Bowel Oxidative Stress in the Maternal Separation Animal Model

Selegiline Ameliorates Depression-Like Behavior in Mice Lacking the CD157/BST1 Gene, a Risk Factor for Parkinson’s Disease

Involvement of Oxytocin Receptor/Erk/MAPK Signaling in the mPFC in Early Life Stress-Induced Autistic-Like Behaviors

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