Role of 5-hydroxytryptamine type 3 receptors in the regulation of anxiety reactions / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

5-Hydroxytryptamine (5-HT) type 3 receptor (5-HT3R) is the only type of ligand-gated ion channel in the 5-HT receptor family. Through the high permeability of Na+, K+, and Ca2+ and activation of subsequent voltage-gated calcium channels (VGCCs), 5-HT3R induces a rapid increase of neuronal excitability or the release of neurotransmitters from axon terminals in the central nervous system (CNS). 5-HT3Rs are widely expressed in the medial prefrontal cortex (mPFC), amygdala (AMYG), hippocampus (HIP), periaqueductal gray (PAG), and other brain regions closely associated with anxiety reactions. They have a bidirectional regulatory effect on anxiety reactions by acting on different types of cells in different brain regions. 5-HT3Rs mediate the activation of the cholecystokinin (CCK) system in the AMYG, and the γ‍-aminobutyric acid (GABA) "disinhibition" mechanism in the prelimbic area of the mPFC promotes anxiety by the activation of GABAergic intermediate inhibitory neurons (IINs). In contrast, a 5-HT3R-induced GABA "disinhibition" mechanism in the infralimbic area of the mPFC and the ventral HIP produces anxiolytic effects. 5-HT2R-mediated regulation of anxiety reactions are also activated by 5-HT3R-activated 5-HT release in the HIP and PAG. This provides a theoretical basis for the treatment of anxiety disorders or the production of anxiolytic drugs by targeting 5-HT3Rs. However, given the circuit specific modulation of 5-HT3Rs on emotion, systemic use of 5-HT3R agonism or antagonism alone seems unlikely to remedy anxiety, which deeply hinders the current clinical application of 5-HT3R drugs. Therefore, the exploitation of circuit targeting methods or a combined drug strategy might be a useful developmental approach in the future.

Effect of Paeoniae Alba Radix extract on 5-HT3 receptor pathway in primarily cultured rat hippocampal neurons / 中草药

Objective: To investigate the effects of Paeoniae Alba Radix extracts (PAREs) on 5-HT3R mediated ion channels in primarily cultured hippocampal neurons of rats with depression. Methods: An animal model of depression was successfully developed and evaluated in rats. PARE was used for drug intervention. Serum in each group was collected, inactivated and then added into the primary hippocampal neurons for 24 h. The protein expression levels of 5-HT3AR and 5-HT3BR in the neurons of each group were examined by Western blotting (WB). The 5-HT3R channel current was recorded by a whole-cell patch clamp. Results: Compared with normal rats, the rats with depression had significantly reduction in total distance of the open-field test (OFT) and sucrose preference ratio (P < 0.01). The hippocampal neurons treated with serum of depressive rats had significantly increased protein expression of 5-HT3AR and 5-HT3BR (P < 0.05) and current density value (P < 0.05) compared to those treated with normal rat serum. Compared with the depressive rats, the rats treated with PARE and fluoxetine had significantly increased OFT (P < 0.05) and sucrose preference ratio (P < 0.01). The primary hippocampal neurons cultured with serum from PARE and fluoxetine-treated rats had significantly reduction in protein expression of 5-HT3AR and 5-HT3BR (P < 0.05, 0.01, 0.001) and current density value (P < 0.01). Conclusion: PARE can reduce the 5-HT3R ion channel current density in the rats with depression. This may be its central mechanism in treating depression.

Effect of Radix Bupleuri Extract on 5-HT3R Pathway in Primarily Cultured Rat Hippocampal Neurons / 世界科学技术-中医药现代化

This study was aimed to investigate the effect of Radix Bupleuri extract (RBE) on 5-HT3R channel currents of primarily cultured hippocampal neurons in depression emotion rats.Depression emotion model ratswere duplicated.RBE was used for drug intervention.And then,the rats were evaluated by the open-field test (OFT) and the sucrose preference test.Serum of rats in each group was collected and then added into the primary cultured hippocampal neurons for 24 h.The 5-HT3R channel currents were recorded by the whole-cell patch clamp.The results showed that compared with the normal group,the total score of OFT in the model group was significantly decreased (P < 0.01); the sucrose preference ratio decreased obviously (P < 0.01); and the current density value of primary cultured hippocampal neurons in serum of the model group was significantly higher (P <0.01).Compared with the model group,the total scores of OFT in the RBE group and fluoxetine group increased significantly (P < 0.05,P < 0.01); the sucrose preference ratio also increased obviously (P < 0.05,P < 0.05); and current density value of the primary cultured hippocampal neurons in serum of the RBE group and fluoxetine group decreased significantly (P < 0.01,P < 0.01).It was concluded that RBE can effectively correct the abnormal 5-HT3R channel currents of rats with depression emotion,which may be one of the central mechanisms in the treatment of depression emotion.

Seizure developed after palonosetron intravenous injection during recovery from general anesthesia: A case report / 대한마취과학회지

Seizure associated with antiemetics is rare. We report seizure associated with a 5-HT3 receptor antagonist in a 38 years old female. The patient underwent ureterorenoscopic lithotripsy due to left upper ureter stone. After operation, the patient complained of nausea in the postanesthetic recovery unit. In order to subside symptom, the patient was administrated 5-HT3 receptor antagonist, palonosetron, 0.075 mg intravenously. Shortly after administration of that, the patient developed generalized tonic-clonic seizures. The symptom was subsided after midazolam and thiopental sodium were injected. But 40 minutes later, seizure recurred and subsided with midazolam again. The patient recovered completely without any specific sequelae.