Short-Term Consequences of Single Social Defeat on Accumbal Dopamine and Behaviors in Rats

Nemets, Vsevolod V.; Deal, Aaron; Соболев, В. Е.; Grinevich, Vladimir P.; Gainetdinov, Raul R.; Budygin, Evgeny A.

doi:10.3390/biom13010035

Cited by 4 publications

(1 citation statement)

References 73 publications

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“…While these results resemble the effects of defeat in the signaling pathway, it is worth noting that CREB and the MAPK pathway are also regulated by systems previously reported to respond to social defeat. For instance, social defeat elicits increased dopamine release in the NAc ( Tidey and Miczek, 1996 ; Nemets et al, 2022 ), and dopamine receptors are known to affect MAPK and CREB phosphorylation ( Wang H. et al, 2018 ). Therefore, future studies should explore cell-specific changes in the NAc driving the observed changes in these markers.…”

Section: Discussionmentioning

confidence: 99%

Limbic oxytocin receptor expression alters molecular signaling and social avoidance behavior in female prairie voles (Microtus ochrogaster)

Nerio-Morales,

Boender,

Young

et al. 2024

Front. Neurosci.

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IntroductionThe social defeat paradigm is the most representative animal model to study social anxiety disorder (SAD) and its underlying neuronal mechanisms. We have previously reported that defeat progressively reduces oxytocin receptors (OXTR) in limbic regions of the brain over an eight-week period in female prairie voles (Microtus ochrogaster). Oxytocin receptors activate the mitogen-activated protein kinase (MAPK) pathway, which has been previously associated with the anxiolytic effects of oxytocin. Here, we assessed the functional significance of OXTR in stress-induced social avoidance and the response of the MAPK signaling pathway in the nucleus accumbens (NAc), anterior cingulate cortex (ACC), and basolateral amygdala (BLA) of female prairie voles.MethodsIn experiment 1, Sexually naïve adult female prairie voles were defeated for three consecutive days and tested a week after for social preference/avoidance (SPA) test. Control subjects were similarly handled without defeat conditioning. In experiment 2, sexually and stress naïve adult female prairie voles were bilaterally injected into the NAc, ACC, or the BLA with a CRISPR/Cas9 virus targeting the Oxtr coding sequence to induce OXTR knockdown. Two weeks post-surgery, subjects were tested for SPA behavior. Viral control groups were similarly handled but injected with a control virus. A subgroup of animals from each condition in both experiments were similarly treated and euthanized without being tested for SPA behavior. Brains were harvested for OXTR autoradiography, western blot analysis of MAPK proteins and quantification of local oxytocin content in the NAc, BLA, ACC, and PVN through ELISA.ResultsSocial defeat reduced OXTR binding in the NAc and affected MAPK pathway activity and oxytocin availability. These results were region-specific and sensitive to exposure to the SPA test. Additionally, OXTR knockdown in the NAc, ACC, and BLA induced social avoidance and decreased basal MAPK activity in the NAc. Finally, we found that OXTR knockdown in these regions was associated with less availability of oxytocin in the PVN.ConclusionDysregulation of the oxytocin system and MAPK signaling pathway in the NAc, ACC, and BLA are important in social behavior disruptions in female voles. This dysregulation could, therefore, play an important role in the etiology of SAD in women.

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Section: Discussionmentioning

confidence: 99%

Limbic oxytocin receptor expression alters molecular signaling and social avoidance behavior in female prairie voles (Microtus ochrogaster)

Nerio-Morales,

Boender,

Young

et al. 2024

Front. Neurosci.

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How it ends: A review of behavioral and psychological phenomena, physiological processes and neural circuits in the termination of aggression in other animals and anger in people

Potegal

2024

Behavioural Brain Research

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Trace amine-associated receptor 1 agonist reduces aggression in brain serotonin-deficient tryptophan hydroxylase 2 knockout rats

Zhukov,

Alnefeesi,

Krotova

et al. 2024

Front. Psychiatry

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IntroductionAggression and self-harm disproportionately occur in youths preoccupied with social status tracking. These pathological conditions are linked to a serotonin (5-HT) deficit in the brain. Ablation of 5-HT biosynthesis by tryptophan hydroxylase 2 knockout (TPH2-KO) increases aggression in rodents. Remarkably, deletion of the trace amine-associated receptor 1 (TAAR1) results in the same consequences. Unlike the nuanced dynamics of social status cues in young people, the social ranks of rats mainly advance when they dominate larger opponents in combat.MethodsThis study explored whether the potent TAAR1 agonist RO5263397 reduces aggression caused by 5-HT depletion, and whether social rank advancement motivates this aggression. The resident-intruder paradigm was applied with larger and smaller intruders to evaluate whether social rank advancement motivates aggressive behaviors in TPH2-KO rats.ResultsWhen a smaller intruder was introduced, 5-HT-deficient rats did not differ from wild type littermates. However, when the intruders were larger, the mutants extended their aggressive efforts, refusing to submit. Importantly, RO5263397 selectively abolished this abnormal form of aggression in TPH2-KO rats.DiscussionResults supported social rank advancement as the main incentive. These data also suggest that TAAR1 is a promising target for the development of new treatments for aggression; independent data also support this conclusion.

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Short-Term Consequences of Single Social Defeat on Accumbal Dopamine and Behaviors in Rats

Cited by 4 publications

References 73 publications

Limbic oxytocin receptor expression alters molecular signaling and social avoidance behavior in female prairie voles (Microtus ochrogaster)

Limbic oxytocin receptor expression alters molecular signaling and social avoidance behavior in female prairie voles (Microtus ochrogaster)

How it ends: A review of behavioral and psychological phenomena, physiological processes and neural circuits in the termination of aggression in other animals and anger in people

Trace amine-associated receptor 1 agonist reduces aggression in brain serotonin-deficient tryptophan hydroxylase 2 knockout rats

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