Targeting PSD95/nNOS by ZL006 alleviates social isolation-induced heightened attack behavior in mice.
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.
['Yang|Luqi|L|', 'Cui|Jingyu|J|', 'Zeng|Ligong|L|', 'Lu|Wen|W|http://orcid.org/0000-0003-1826-5720']
ZL006 Social isolation (SI) Nitric oxide (NO) Neuronal nitric oxide synthase (nNOS) Postsynaptic density 95 (PSD95) Resident–intruder test