Repeated experience of social defeats increases serotonin transporter and monoamine oxidase A mRNA levels in raphe nuclei of male mice

Филипенко, М. Л.; Beilina, Alexandra; Alekseyenko, Olga V.; Dolgov, Vadim V.; Kudryavtseva, N. N.

doi:10.1016/s0304-3940(01)02495-8

Cited by 54 publications

(38 citation statements)

References 15 publications

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“…Elevated MAO-A level in these regions in MDE is consistent with other specific findings: MDE is a highstress state, and glucocorticoid administration increases transcription rate and catalytic activity of MAO-A in human neuroblastoma and glioblastoma cell lines (Ou et al, 2006a). Furthermore, glucocorticoid administration and/or chronic stress increase MAO-A mRNA and/or MAO-A protein levels in the PFC of rodents (Filipenko et al, 2002;Slotkin et al, 1998). In humans, during MDE, greater whole-brain serotonin turnover has been reported (Barton et al, 2008) and this is consistent with greater MAO-A level and/or activity as MAO-A is the primary route of serotonin metabolism in brain.…”

Section: Introductionsupporting

confidence: 89%

Elevated Monoamine Oxidase A Binding During Major Depressive Episodes Is Associated with Greater Severity and Reversed Neurovegetative Symptoms

Chiuccariello

Houle

Miler

et al. 2013

Neuropsychopharmacol

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Inadequate treatment response occurs in approximately 40% of major depressive episodes (MDEs), and one approach to solve this is careful matching of treatment to the specific pathologies of MDE. One such biological abnormality is elevated monoamine oxidase A (MAO-A) levels, which occurs in the prefrontal and anterior cingulate cortex (PFC and ACC) during MDE; however, the subtypes for which this abnormality is most prominent are unknown. We hypothesized that MAO-A levels in the PFC and ACC are most elevated in MDE with greater severity and reversed neurovegetative symptoms (hypersomnia and either hyperphagia or weight gain). MAO-A V T (an index of MAO-A density) was measured using [ 11 C]harmine positron emission tomography (PET) in 42 subjects with MDEs secondary to major depressive disorder and 37 healthy controls. The effect of severity and reversed neurovegetative symptoms on MAO-A V T in the PFC and ACC was analyzed using a multivariate analysis of variance (MANOVA). Greater severity and reversed neurovegetative symptoms were associated with elevated MAO-A V T in the PFC and ACC (MANOVA, severity: F (2,38) ¼ 5.44, p ¼ 0.008; reversed neurovegetative symptoms: F (2,38) ¼ 5.13, p ¼ 0.01). Increased MAO-A level, when greater severity and reversed neurovegetative symptoms are present, may explain the association of these clinical features with a preferential response to MAO inhibitors, which is especially well-evidenced for reversed neurovegetative symptoms in MDE. As MAO-A creates oxidative stress, facilitates apoptosis, and metabolizes monoamines, therapeutics opposing these processes are predicted to best treat MDE with greater severity and reversed neurovegetative symptoms.

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Section: Introductionsupporting

confidence: 89%

Elevated Monoamine Oxidase A Binding During Major Depressive Episodes Is Associated with Greater Severity and Reversed Neurovegetative Symptoms

Chiuccariello

Houle

Miler

et al. 2013

Neuropsychopharmacol

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“…There is a report that strong chronic stress, such as a social defeat stress upregulates the expression of monoamine oxidase-A (MAO-A) gene to accelerate the neurotransmitter degeneration. 23) In this point of the increased metabolite, our result was consistent with the previous reports which the elevation of 5-HIAA was observed in the amygdala of mice in the very stressed situation. 2,24) Taken together, repeated electric footshock impaired motivation-related lever press behavior accompanied with changing the 5-HTergic system in the amygdale of mice.…”

Section: Discussionsupporting

confidence: 93%

Dynorphin A (1–13) Alleviated Stress-Induced Behavioral Impairments in Mice

Mamiya

Hasegawa

Hiramatsu

2014

Biological & Pharmaceutical Bulletin

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In this study we investigated whether κ-opioid receptor stimulation by dynorphin A (1-13), a potent fragment of endogenous peptide, attenuated repeated stress-induced behavioral impairments in mice. In order to reduce the motivation to escape, mice were preexposed to inescapable electric footshock (day 0), and then dynorphin A (1-13) was administered to mice prior to the stress from the next day for 4 d (days 1-4). Dynorphin A (1-13) (1500 pmol/5 µL intracerebroventricular (i.c.v.)) attenuated the repeated stress-induced escape failures from the shock, and this improvement was inhibited by the pretreatment of nor-binaltorphimine (4.9 nmol/kg subcutaneously (s.c.)), a κ-opioid receptor antagonist. In the neurochemical experiments, we detected an increase in 5-hydroxyindoleacetic acid (5-HIAA) content, but not in serotonin (5-HT) content, and an increase in the 5-HIAA/5-HT ratio was observed in the amygdala of the group with footshock compared with the group without shock. Additionally, the changes in 5-HIAA content and the ratio were reversed by dynorphin A (1-13). However, there were no differences in 5-HT or 5-HIAA content or their ratios in the hippocampus among the three groups. These results suggest that dynorphin might alleviate the stress-induced behavioral impairments accompanied by regulation of the 5-HTergic system in the brain.Key words dynorphin; κ-opioid receptor; repeated stress; amygdala; serotonin The number of patients presenting with stress-induced behavioral abnormality is increasing in Japan as well as other developed countries, and thus it is very important to find a cure. Stress-induced behavioral abnormality in rodent is widely employed as a model of mood disorders.1) In the paradigm adopted in this study, i.e., the learned helplessness task, exposure to an uncontrollable aversive stimulus leads to a decreased ability to escape from subsequent aversive situations. Pre-exposure to inescapable electric footshock stress leads to a high escape failure rate in subsequent learning trials. This model is being used increasingly to investigate the neurobiology of affective illness and to explore candidates for medicines that relieve stress, 2) such as antidepressants which activate serotonergic system. In addition, many studies have revealed that the amygdala/hippocampus as well as the frontal cortex play a critical role in controlling such repeated aversive stress directly and/or indirectly.3,4) Therefore, we focus on the serotonergic system in the amygdala/hippocampus.Opioid systems in the brain are known to control mood function and pain.5) Opioid peptides and their receptors are found at high concentrations in regions of the limbic system. However, their involvement in the pathogenesis of mood disorders, particularly depressive illness, remains an enigma. Accumulating evidence from animal research has revealed that μ-, δ-, and κ-opioid receptors distinctly control mood-related processes. Delta-opioid receptor agonists show promise as antidepressants, whereas μ-opioid receptor agonists are charac...

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“…(23,24) Possibly of more direct relevance to studies on the ''cycle of violence'' is the evidence that social stress and defeats in aggressive confrontations have a direct effect by increasing transcription of both MAOA and SERT in the brain of CBA/Lac male mice. (25) This may reflect a compensatory response to activation of the serotonergic system stimulated by the social stress. Overall, the data from rodents suggest that stress engenders mechanisms implicating the HPA axis and serotonin turnover, which have important short-term behavioural effects, but which also have homeostatic consequences attempting to protect against longer term damaging outcomes.…”

Section: Pre-synaptic Neuronmentioning

confidence: 99%

“…(80) Although the picture is complicated by the variable responses in different brain areas, it could be speculated that elevation of the transcription factor c-fos may in turn be one of the factors responsible for the upregulation of the MAOA and SERT genes observed in chronic stress. (25) To date, there have been no direct attempts to investigate this; however, a search of the MAOA sequence reveals a cluster of c-fos-binding sites (AP1) in intron 10. While the consensus-binding1 site for c-fos (GAGTCA) has an expected frequency of about 1 per 4,000 bp, this cluster of seven sites in intron 10 is compressed into a 6,700 bp segment.…”

Section: Maoa Variants and Antisocial/ Aggressive Behavioursmentioning

confidence: 99%

The importance of stress and genetic variation in human aggression

Craig

2007

BioEssays

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Both genetic and environmental factors have key roles in determining aggressive tendencies. In particular, reaction to stress appears to be an important factor in precipitating aggressive episodes and individuals may vary in their ability to cope with stressful environments depending on their genetic make up. Evidence from humans and primates indicates that adverse rearing conditions may interact with variants in stress and neurotransmitter pathway genes leading to antisocial and/or violent behaviour. Common alleles of some serotonin pathway genes, including those involved in its degradation (monoamine oxidase A, MAOA), or its re-uptake into pre-synaptic neurones (serotonin transporter, SERT) have been shown to confer functional variation. Examination of the interaction between the alleles of such polymorphisms (in particular those affecting MAOA) and environmental stressors suggest that they may provide protection against, or increase sensitivity to, abusive upbringing; an observation that may explain part of the variability in developmental outcomes associated with maltreatment.

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Repeated experience of social defeats increases serotonin transporter and monoamine oxidase A mRNA levels in raphe nuclei of male mice

Cited by 54 publications

References 15 publications

Elevated Monoamine Oxidase A Binding During Major Depressive Episodes Is Associated with Greater Severity and Reversed Neurovegetative Symptoms

Elevated Monoamine Oxidase A Binding During Major Depressive Episodes Is Associated with Greater Severity and Reversed Neurovegetative Symptoms

Dynorphin A (1–13) Alleviated Stress-Induced Behavioral Impairments in Mice

The importance of stress and genetic variation in human aggression

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