Sinapic acid balances the excitatory and inhibitory neurotransmitter systems to mitigate post-traumatic stress...

Post-traumatic stress disorder (PTSD) is a mental illness that can occur in individuals who have experienced trauma. Sinapic acid has been reported to be effective for anxiety as a GABA_A receptor agonist, and has been reported to improve cognitive impairment by modulating the GABA/glutamate ratio, but there are no reports associated with PTSD. In the present study, we investigated the effects of sinapic acid in a mouse model of PTSD induced by a single prolonged stress (SPS) protocol. We examined the therapeutic effects of sinapic acid on emotional and cognitive impairment in the SPS mouse model. We also explored the effects of sinapic acid on fear memory extinction. Western blot was employed to investigate how sinapic acid exerts its pharmacological activities. Sinapic acid ameliorated PTSD-like behaviors in a SPS mouse model. Notably, in the case of cognitive dysfunction, paroxetine failed to improve, but sinapic acid restored cognitive function. Additionally, sinapic acid did not increase locomotor behavior, while paroxetine increased. Furthermore, sinapic acid normalized the overactivated GluN2B-containing NMDA receptor signaling pathway in the amygdala and the hypothalamus. The mitigation of fear memory deficits by sinapic acid was exerted by sub-effective dose of GluN2B-containing NMDA receptor antagonist and abolished by GABA_A receptor antagonist. Our findings suggest that sinapic acid could serve as a potential therapeutic agent for PTSD by balancing excitatory and inhibitory neurotransmitter systems due to its action on GluN2B-containing NMDA receptors and GABA_A receptors.