GABABR1 in DRN mediated GABA to regulate 5-HT expression in multiple brain regions in male rats with high and low aggressive behavior

Liu, Xiaoju; Wang, Haijuan; Wang, Xiaoyu; Ning, Yin-xia; Gao, Jie

doi:10.1016/j.neuint.2021.105180

Cited by 2 publications

(8 citation statements)

References 104 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies have demonstrated that 5-HT neurons in the DRN have nerve fiber connections with the PFC, hypothalamus, and hippocampus [ 37 ]. Consequently, the expression and nerve connection of 5-HT neurons and GB1 in the DRN, as well as the nerve fiber connection of BXD (regulates AO) and SY (regulates AI).…”

Section: Resultsmentioning

confidence: 99%

“…They can instinctively attack invaders, to protect their territory and generate hostile psychology and behavior. Previous studies have reported that social isolation combined with the resident-intruder paradigm could successfully prepare a scientific and stable rat model of high-aggressive and low-aggressive behavior [ 37 ]. Meanwhile, AO and AI rat models were successfully replicated in this paper, laying the foundation for subsequent experiments.…”

Section: Discussionmentioning

confidence: 99%

“…Many studies have demonstrated that 5-HT is a key neurotransmitter that regulates anger attacks, and depression patients with anger are more prone to 5-HT imbalance than patients without anger [ 34 , 37 , 72 , 73 ]. Decreased levels of 5-HT or 5-HIAA in brain tissue can increase the occurrence of aggressive behavior and violence [ 74 ].…”

Section: Discussionmentioning

confidence: 99%

“…GABA can seriously affect the function of the PFC [84] and participate in the regulation of emotional disorders [40]. 5-HT and GABA levels have synaptic connections and regulate each other [37,[85][86][87]. Various pathological processes, including chronic pain, epilepsy, and schizophrenia, are often accompanied by changes in GB1 expression and function [88,89].…”

Section: Possible Action Targets and Mechanism Of Bxd Against Ao And ...mentioning

confidence: 99%

“…Numerous studies have demonstrated that various neurotransmitters and hormones, including serotonin (5-HT), norepinephrine, dopamine, androgens, and estrogens play a role in anger regulation, with 5-HT being the most important [ 34 , 35 ]. Major serotonergic populations contained in the midbrain dorsal raphe and median raphe nuclei, then projecting to various regions of the brain such as the PFC, hippocampus, and hypothalamus [ 36 , 37 ], participate in regulating cognition, intuition, and emotion [ 38 ]. The study demonstrated that depressed patients who experience anger episodes may have relatively greater serotonin dysregulation than depressed patients without these episodes [ 27 ].…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Baixiangdan capsule and Shuyu capsule regulate anger-out and anger-in, respectively: GB1–mediated GABA can regulate 5-HT levels in multiple brain regions

Liu

Wang

et al. 2023

Aging

Self Cite

View full text Add to dashboard Cite

The identity of the mechanism by which the Baixiangdan capsule (BXD) and the Shuyu capsule (SY) control anger-out (AO) and anger-in (AI) in rodents is unclear. The current study clarified the intervention role of BXD and SY on AO and AI male rats. We further explored the differences between BXD and SY in the treatment of AO and AI rats. Social isolation combined with the resident-intruder paradigm was used to establish the angerout and AI rats models. On this basis, GABA content in the dorsal raphe nucleus (DRN) and serotonin (5-HT) contents in these brain regions were detected using ELISA after various time courses (0, 1, 3, 5, and 7 days) treated with BXD and SY. Co-expression of 5-HT and GB1 in the DRN was detected. GB1-specific agonist baclofen and GB1-specific inhibitor CGP35348 were injected into the DRN. Changes in 5-HT levels in these brain regions were then detected. After treatment, rats in the BXD group exhibited lower aggressive behavior scores, longer latencies of aggression, lower total distances in the open field test, and a higher sucrose preference coefficient. Meanwhile, rats in the SY group exhibited higher aggressive behavior scores, shorter latencies of aggression, higher total distances in the open field test, and higher sucrose preference coefficients. With increasing medication duration, 5-HT levels in these brain regions were increased gradually, whereas GABA levels in the DRN were decreased gradually, and all recovered to normal levels by the 7th day. A large number of 5-HT-positive cells could be found in the immunofluorescence section in the DRN containing GABABR1 (GB1)positive cells, indicating that 5-HT neurons in the DRN co-expressed with GB1. Furthermore, after the drug intervention, the 5-HT level in the DRN was elevated to a normal level, and the GB1 level in the DRN was decreased to a normal level. After the microinjection of baclofen into the DRN, the 5-HT contents in these brain regions were decreased. By contrast, the 5-HT contents were increased after injection with CGP35348. BXD and SY could effectively improve the abnormal behavior changes of AO and AI rats, and the optimal duration of action was 7 days. The improvement way is as follows: Decreased abnormal increase of GABA and GB1 in the DRN further mediated synaptic inhibition and increased 5-HT level in the DRN, leading to increased 5-HT levels in the PFC, hypothalamus, and hippocampus. Therefore, GB1-mediated GABA in the DRN could regulate 5-HT levels in these brain regions, which may be one of the ways by which BXD and SY treat AO and AI, respectively.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Possible Action Targets and Mechanism Of Bxd Against Ao And ...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Baixiangdan capsule and Shuyu capsule regulate anger-out and anger-in, respectively: GB1–mediated GABA can regulate 5-HT levels in multiple brain regions

Liu

Wang

et al. 2023

Aging

Self Cite

View full text Add to dashboard Cite

show abstract

Role of the Dorsal Raphe Nucleus in Pain Processing

Zhang,

Li,

Zhang

et al. 2024

Brain Sciences

View full text Add to dashboard Cite

The dorsal raphe nucleus (DRN) has gained attention owing to its involvement in various physiological functions, such as sleep–awake, feeding, and emotion, with its analgesic role being particularly significant. It is described as the “pain inhibitory nucleus” in the brain. The DRN has diverse projections from hypothalamus, midbrain, and pons. In turn, the DRN is a major source of projections to diverse cortex, limbic forebrain thalamus, and the midbrain and contains highly heterogeneous neuronal subtypes. The activation of DRN neurons in mice prevents the establishment of neuropathic, chronic pain symptoms. Chemogenetic or optogenetic inhibition neurons in the DRN are sufficient to establish pain phenotypes, including long-lasting tactile allodynia, that scale with the extent of stimulation, thereby promoting nociplastic pain. Recent progress has been made in identifying the neural circuits and cellular mechanisms in the DRN that are responsible for sensory modulation. However, there is still a lack of comprehensive review addressing the specific neuron types in the DRN involved in pain modulation. This review summarizes the function of specific cell types within DRN in the pain regulation, and aims to improve understanding of the mechanisms underlying pain regulation in the DRN, ultimately offering insights for further exploration.

show abstract

GABABR1 in DRN mediated GABA to regulate 5-HT expression in multiple brain regions in male rats with high and low aggressive behavior

Cited by 2 publications

References 104 publications

Baixiangdan capsule and Shuyu capsule regulate anger-out and anger-in, respectively: GB1–mediated GABA can regulate 5-HT levels in multiple brain regions

Baixiangdan capsule and Shuyu capsule regulate anger-out and anger-in, respectively: GB1–mediated GABA can regulate 5-HT levels in multiple brain regions

Role of the Dorsal Raphe Nucleus in Pain Processing

Contact Info

Product

Resources

About