Effect of chronic social defeat stress on behaviors and dopamine receptor in adult mice

Huang, Guang‐Biao; Zhao, Tong; Gao, Xiaoxi; Zhang, Hongxing; Xu, Yuming; Li, Hao; Lv, Luxian

doi:10.1016/j.pnpbp.2015.12.002

Cited by 43 publications

(31 citation statements)

References 30 publications

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“…This may suggest that dopamine modulates the interaction between cortical activity following stress exposure, and hippocampal frequency-dependent synaptic plasticity. Indeed, a recent study has shown that decreases in dopamine D1 receptors within the prefrontal cortex are associated with increased social avoidance after social defeat stress (Huang et al., 2016). Not surprisingly, because the hippocampus is important for learning and memory processes, this study also showed that social stress led to impaired recognition memory, in a somewhat similar fashion as in D1 knockout mice (El-Ghundi et al., 1999).…”

Section: Discussionmentioning

confidence: 99%

Social defeat stress induces depression-like behavior and alters spine morphology in the hippocampus of adolescent male C57BL/6 mice

Iñiguez

Aubry

Riggs

et al. 2016

Neurobiology of Stress

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Social stress, including bullying during adolescence, is a risk factor for common psychopathologies such as depression. To investigate the neural mechanisms associated with juvenile social stress-induced mood-related endophenotypes, we examined the behavioral, morphological, and biochemical effects of the social defeat stress model of depression on hippocampal dendritic spines within the CA1 stratum radiatum. Adolescent (postnatal day 35) male C57BL/6 mice were subjected to defeat episodes for 10 consecutive days. Twenty-four h later, separate groups of mice were tested on the social interaction and tail suspension tests.Hippocampi were then dissected and Western blots were conducted to quantify protein levels for various markers important for synaptic plasticity including protein kinase M zeta (PKMζ), protein kinase C zeta (PKCζ), the dopamine-1 (D1) receptor, tyrosine hydroxylase (TH), and the dopamine transporter (DAT). Furthermore, we examined the presence of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-receptor subunit GluA2 as well as colocalization with the post-synaptic density 95 (PSD95) protein, within different spine subtypes (filopodia, stubby, long-thin, mushroom) using an immunohistochemistry and Golgi-Cox staining technique. The results revealed that social defeat induced a depression-like behavioral profile, as inferred from decreased social interaction levels, increased immobility on the tail suspension test, and decreases in body weight. Whole hippocampal immunoblots revealed decreases in GluA2, with a concomitant increase in DAT and TH levels in the stressed group. Spine morphology analyses further showed that defeated mice displayed a significant decrease in stubby spines, and an increase in long-thin spines within the CA1 stratum radiatum. Further evaluation of GluA2/PSD95 containing-spines demonstrated a decrease of these markers within long-thin and mushroom spine types. Together, these results indicate that juvenile social stress induces GluA2- and dopamine-associated dysregulation in the hippocampus – a neurobiological mechanism potentially underlying the development of mood-related syndromes as a consequence of adolescent bullying.

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Section: Discussionmentioning

confidence: 99%

Social defeat stress induces depression-like behavior and alters spine morphology in the hippocampus of adolescent male C57BL/6 mice

Iñiguez

Aubry

Riggs

et al. 2016

Neurobiology of Stress

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“…[96]) and the light/dark preference test (e.g. [98]). It is possible that the lack of difference in anxiety between resilient and susceptible animals stems from the large within-group variability.…”

Section: Discussionmentioning

confidence: 99%

Indomethacin counteracts the effects of chronic social defeat stress on emotional but not recognition memory in mice

2017

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We have previously observed the impairing effects of chronic social defeat stress (CSDS) on emotional memory in mice. Given the relation between stress and inflammatory processes, we sought to study the effectiveness of the anti-inflammatory indomethacin in reversing the detrimental effects of CSDS on emotional memory in mice. The effects of CSDS and indomethacin on recognition memory were also evaluated. Male CD1 mice were randomly divided into four groups: non-stressed + saline (NS+SAL); non-stressed + indomethacin (NS+IND); stressed + saline (S+SAL); and stressed + indomethacin (S+IND). Stressed animals were exposed to a daily 10 min agonistic confrontation (CSDS) for 20 days. All subjects were treated daily with saline or indomethacin (10 mg/kg, i.p.). 24 h after the CSDS period, all the mice were evaluated in a social interaction test to distinguish between those that were resilient or susceptible to social stress. All subjects (n = 10–12 per group) were then evaluated in inhibitory avoidance (IA), novel object recognition (NOR), elevated plus maze and hot plate tests. As in control animals (NS+SAL group), IA learning was observed in the resilient groups, as well as in the susceptible mice treated with indomethacin (S+IND group). Recognition memory was observed in the non-stressed and the resilient mice, but not in the susceptible animals. Also, stressed mice exhibited higher anxiety levels. No significant differences were observed in locomotor activity or analgesia. In conclusion, CSDS induces anxiety in post-pubertal mice and impairs emotional and recognition memory in the susceptible subjects. The effects of CSDS on emotional memory, but not on recognition memory and anxiety, are reversed by indomethacin. Moreover, memory impairment is not secondary to the effects of CSDS on locomotor activity, emotionality or pain sensitivity.

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“…Differences in susceptibility to engage in depression-like behavior following repeated social defeat may be mediated by the dopamine D 1 receptor (Huang et al 2016). Pre-defeat treatment with raclopride, a D 2 -receptor antagonist, or SCH 23390, a D 1 -receptor antagonist, blocked defeat-induced potentiation of conditioned place preference for cocaine, implicating signaling at both receptors in the pathogenesis of social defeat effects (Montagud-Romero et al 2016).…”

Section: Discussionmentioning

confidence: 99%

“…In terms of understanding the neurobiological substrates of defeat effects, acute stress is known to alter the striatal circuitry that subserves reward (Porcelli et al 2012), and dopaminergic transmission previously has been shown to mediate the long-term effects of stress on reward (Montagud-Romero et al 2016, Huang et al 2016). Social defeat in adolescence leads to long-term changes in dopaminergic pathways studied in adulthood (Watt et al 2014, Burke et al 2013), a finding that could be interpreted as developmental in nature.…”

Section: Introductionmentioning

confidence: 99%

Modeling hypohedonia following repeated social defeat: Individual vulnerability and dopaminergic involvement

Spierling

Mattock

Zorrilla

2017

Physiology & Behavior

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Social defeat in rodents putatively can model hypohedonia. The present studies examined models for assessing hypohedonia-like behavior and tested the hypotheses that 1) individual differences in baseline reward sensitivity predict vulnerability, and 2) defeat elicits changes in pharmacological measures of striatal dopaminergic function. Male Wistar rats (n=142) received repeated defeat (3 “triad” blocks of 3 defeats) or control handling. To determine whether defeat influenced consumption of SuperSac (glucose-saccharin) over an isocaloric, less preferred, glucose solution, a 2-choice paradigm was used. To determine repeated defeat effects on the reinforcing efficacy of SuperSac, a progressive-ratio schedule of reinforcement was used. Amphetamine-induced locomotor activity (0.08 mg/kg, s.c.) was determined as a measure sensitive to striatal dopaminergic function. Defeat reduced SuperSac consumption during the first two triads—an effect seen in the third triad only in defeated rats with High vs. Low baseline SuperSac intake. The characteristic escalation in PR breakpoint for SuperSac normally seen in controls was absent in defeated rats, leading to a significant difference by the third triad. Defeat-induced blunting of the escalation in PR performance was greater in rats with High antecedent PR breakpoints and persisted 2.5 weeks post-defeat. Repeated defeat also blunted amphetamine-induced locomotion 13 days post-defeat. Thus, hypohedonic-like effects of social defeat were detected and accompanied by persistently attenuated striatal dopamine function. Early effects were seen for consumption of differentially-palatable solutions, and persistent effects were seen for the “breakpoint” motivational measure. The results implicate initial reward sensitivity as a risk factor for stress-induced hypohedonia.

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Effect of chronic social defeat stress on behaviors and dopamine receptor in adult mice

Cited by 43 publications

References 30 publications

Social defeat stress induces depression-like behavior and alters spine morphology in the hippocampus of adolescent male C57BL/6 mice

Social defeat stress induces depression-like behavior and alters spine morphology in the hippocampus of adolescent male C57BL/6 mice

Indomethacin counteracts the effects of chronic social defeat stress on emotional but not recognition memory in mice

Modeling hypohedonia following repeated social defeat: Individual vulnerability and dopaminergic involvement

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