The PrLGlu→avBNSTGABA circuit rapidly modulates depression-like behaviors in male mice.
Jie-Ying Chen, Ke Wu, Miao-Miao Guo, Wei Song, Si-Ting Huang, Yong-Mei Zhang
iScience October 20, 2023 DOI: 10.1016/j.isci.2023.107878 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical animal study Peer reviewed |
|---|---|
| Population | Mice exposed to chronic restraint stress with individual housing |
| Interventions | Ketamine chemogenetic activation |
| Topics | Depression |
| Keywords | Anesthesiology |
| Key points | Activating the PrLGlu→avBNSTGABA circuit had antidepressant effects in depression-like mice, with AMPA receptors playing a dominant role. Ketamine rapidly alleviated depression-like behaviors and rescued decreased activity in this circuit, and ketamine's fast behavioral effect was diminished when the circuit was inhibited. The authors propose the circuit as a target for fast regulation of depression. |
Abstract
Depression is a global disease with a high prevalence. Here, we examine the role of the circuit from prelimbic mPFC (PrL) to the anterior ventral bed nucleus of the stria terminalis (avBNST) in depression-like mice through behavioral tests, immunofluorescence, chemogenetics, optogenetics, pharmacology, and fiber photometry. Mice exposed to chronic restraint stress with individual housing displayed depression-like behaviors. Optogenetic or chemogenetic activation of the avBNST-projecting glutamatergic neurons in the PrL had an antidepressant effect. Moreover, we found that α-amino-3-hydroxy-5-methyl-4-isoxazole-propionicacid receptors (AMPARs) play a dominant role in this circuit. Systemic administration of ketamine profoundly alleviated depression-like behaviors in the mice and rapidly rescued the decreased activity in the PrLGlu→avBNSTGABA circuit. Furthermore, the fast-acting effect of ketamine on depressive behaviors was diminished when the circuit was inhibited. To summarize, activating the PrLGlu→avBNSTGABA circuit quickly ameliorated depression-like behaviors. Thus, we propose the PrLGlu→avBNSTGABA circuit as a target for fast regulation of depression.
Comparable studies
Other preclinical and animal studies on depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelics, but Not Ketamine, Produce Persistent Antidepressant-like Effects in a Rodent Experimental System for the Study of Depression Rats | 2020 | Preclinical study | |
| Effects of N,N-Dimethyltryptamine on Rat Behaviors Relevant to Anxiety and Depression Adult male Sprague-Dawley rats | 2018 | Experimental study | |
| A non-hallucinogenic LSD analog with therapeutic potential for mood disorders. Mice and cultured rat cortical neurons | 2023 | Preclinical study | |
| Comparison of (R)-ketamine and lanicemine on depression-like phenotype and abnormal composition of gut microbiota in a social defeat stress model Susceptible mice after chronic social defeat stress | 2017 | Preclinical animal study | |
| 5-HT2ARs Mediate Therapeutic Behavioral Effects of Psychedelic Tryptamines. Rodents | 2023 | Experimental study |