Dataset Information

Targeting PSD95/nNOS by ZL006 alleviates social isolation-induced heightened attack behavior in mice.

ABSTRACT:

Rationale

Deregulated attack behaviors have devastating social consequences; however, satisfactory clinical management for the behavior is still an unmet need so far. Social isolation (SI) has been common during the COVID-19 pandemic and may have detrimental effects on mental health, including eliciting heightened attack behavior.

Objectives

This study aims to explore whether injection of ZL006 can alleviate SI-induced escalation of attack behavior in mice.

Methods

Pharmacological tools, biochemical methods, and behavioral tests were used to explore the potential therapeutic effects of ZL006 targeting postsynaptic density 95 (PSD95)/neuronal nitric oxide synthase (nNOS) pathway on escalation of attack behavior induced by SI in mice.

Results

ZL006 mitigated SI-induced escalated attack behaviors and elevated nitric oxide (NO) level in the cortex of the SI mice. The beneficial effects of ZL006 lasted for at least 72 h after a single injection of ZL006. Potentiation of NO levels by L-arginine blocked the effects of ZL006. Moreover, a sub-effective dose of 7-NI in combination with a sub-effective dose of ZL006 decreased both SI-induced escalated attack behaviors and NO levels in mice subjected to SI.

Conclusions

Our study highlights the importance of the PSD95/nNOS pathway in mediating SI-induced escalation of attack behavior. ZL006 may be a promising therapeutic strategy for treating aggressive behaviors.

SUBMITTER: Yang L

PROVIDER: S-EPMC8521491 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Publications

Targeting PSD95/nNOS by ZL006 alleviates social isolation-induced heightened attack behavior in mice.

Yang Luqi L Cui Jingyu J Zeng Ligong L Lu Wen W

Psychopharmacology 20211018 1

<h4>Rationale</h4>Deregulated attack behaviors have devastating social consequences; however, satisfactory clinical management for the behavior is still an unmet need so far. Social isolation (SI) has been common during the COVID-19 pandemic and may have detrimental effects on mental health, including eliciting heightened attack behavior.<h4>Objectives</h4>This study aims to explore whether injection of ZL006 can alleviate SI-induced escalation of attack behavior in mice.<h4>Methods</h4>Pharmaco ...[more]

PMID: 34661719

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Project description:Psychological stress due to social isolation is known to cause abnormal feeding behaviors, but the influences of gender and aging on subchronic stress-induced changes in feeding behaviors are unknown. Thus, we examined the changes in body weight, food intake, and orexigenic ghrelin-related factors during 2 weeks of isolation stress in young and aged mice. Food intake increased significantly in young mice in the isolation group compared with the group-housed control throughout the experimental period. This isolation-induced increase in food intake was not observed in aged mice. In young mice, there were no significant differences in body weight between the isolated group and group-housed control up to 2 weeks. However, aged male mice exhibited significant weight loss at 2 weeks and a similar tendency was observed in aged female mice. Young male mice, but not female mice, had significantly increased (2.2-fold) plasma acylated ghrelin levels after 1 week of isolation compared with the group-housed control. A significant but lower increase (1.3-fold) was also observed in aged male mice. Hypothalamic preproghrelin gene expression decreased significantly with isolation in young male mice, whereas it increased significantly in female mice. The expression levels of NPY and AGRP in the hypothalamus, which are transmitted by elevated peripheral ghrelin signals, increased significantly in isolated young male mice, whereas the AGRP expression levels decreased significantly in young female mice. Isolation caused no significant differences in the expression levels of these genes in aged mice. In isolation, young female mice exhibited markedly increased dark- and light-phase locomotor activities compared with male mice, whereas male and female aged mice exhibited no obvious increases in activity immediately after the dark phase started. We conclude that the gender-specific homeostatic regulatory mechanisms required to maintain body weight operated during subchronic psychological stress in young mice but not in aged mice.

Dataset Information

Targeting PSD95/nNOS by ZL006 alleviates social isolation-induced heightened attack behavior in mice.

Rationale

Objectives

Methods

Results

Conclusions

Publications

Targeting PSD95/nNOS by ZL006 alleviates social isolation-induced heightened attack behavior in mice.

Similar Datasets

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