Ketamine attenuates the PTSD-like effect via regulation of glutamatergic signaling in the nucleus accumbens of mice.
Muhammad Asim, B. Hao, Abdul Waris, Yilan Liang, Xiao-guang Wang
Molecular and cellular neurosciences March 1, 2022 DOI: 10.1016/j.mcn.2022.103723 (opens in new tab) via Semantic Scholar
Summary
AI-generated from the abstractKetamine infused into the nucleus accumbens (NAc) reduces fear generalization in mice, a core symptom of post-traumatic stress disorder. Foot shock strength-dependently induced fear generalization, increasing c-fos activity, lowering GluR1(S845) and GluR1(S831) protein levels, and raising P-GluN2B protein in the NAc. Local ketamine infusion decreased fear generalization while increasing GluR1(S845) and GluR1(S831) and decreasing P-GluN2B. The findings suggest ketamine may attenuate fear generalization by affecting glutamatergic signaling in the NAc.
Study at a glance
| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Mice |
| Intervention | Ketamine |
| Keywords | Medicine Psychology |
| Key finding | Local infusion of ketamine into the nucleus accumbens decreases fear generalization in mice, associated with increased GluR1(S845) and GluR1(S831) and decreased P-GluN2B protein levels. |
Abstract
Post-traumatic stress disorder (PTSD) is a devastating mental illness with high morbidity and major social and economic burden. Currently, there is no promising therapy available for the treatment of PTSD. Some clinical studies showed that ketamine could effectively alleviate PTSD symptoms. However, it is still unclear which brain region ketamine targets and how it attenuates the PTSD-like effects. In this study, we examined the effect of ketamine on fear generalization (a core symptom of PTSD) by using a mice model of fear generalization induced by fear conditioning procedure. Before retrieval, ketamine was locally infused into the nucleus accumbens (a brain region closely associated with PTSD). Fear generalization mice were subjected to behavioral testing and biochemical assessments, following ketamine infusion. The results showed that the foot shock strength-dependently induced fear generalization in mice with increased c-fos activity, and a lower level of GluR1(S845), GluR1(S831) protein, and a higher level of P-GluN2B protein in the nucleus accumbens (NAc). Local infusion of ketamine into NAc decreased the fear generalization together with an increased level of GluR1(S845), GluR1(S831) protein, and decreased level of P-GluN2B protein. Altogether, these results conclude that ketamine might affect the glutamatergic signaling in the NAc to attenuate the fear generalization in mice.