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      Danshen-Honghua Ameliorates Stress-Induced Menopausal Depression in Rats

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          Abstract

          Objective

          Previously, we have shown that Danshen-Honghua (DSHH) for cognitive deficits after ischemia induced impairments of the hippocampus. Here, we investigate the effects of DSHH on stress-induced depression in menopausal rats.

          Methods

          A rat model with menopausal depression was established with bilateral ovariectomies in female SD rats followed by chronic mild stress treatment for 21 days. 40 rats were randomly divided into the sham surgery group (sham surgery and no stress treatment), surgery group (surgery with no stress treatment), surgery/stress group (surgery and stress treatment), fluoxetine group (2.4 mg·kg −1, with surgery and stress treatment), and DSHH group (35 g·kg −1, with surgery and stress treatment). The rats in the last two groups were treated with stresses together with intragastric drug administration for three weeks after the surgery. Then open-field locomotor scores and sucrose intake were tested for behavior changes. Also, the levels of norepinephrine (NE), dopamine (DA), serotonin (5-HT), and cortisone were determined by high-performance liquid chromatography (HPLC). Serum estradiol (E 2), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were determined by radioimmunoassay.

          Results

          The results of open-field locomotor scores, sucrose intake in both the fluoxetine group and DSHH group, were significantly higher than those of the surgery/stress group ( P < 0.01). Serum LH, FSH, and cortisone levels in both the DSHH group and fluoxetine group were significantly lower than those in the surgery/stress group ( P < 0.01). Serum E 2 levels in these groups were slightly increased in these medicine groups ( P < 0.01). The monoamine levels in the DSHH group were much higher than those in the surgery/stress group ( P < 0.01).

          Conclusion

          DSHH can ameliorate stress-induced depressed syndromes in the surgery/stressed rats via regulating LH and FSH levels as well as monoamine levels.

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          Most cited references22

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          Ketamine blocks bursting in the lateral habenula to rapidly relieve depression

          The N-methyl-d-aspartate receptor (NMDAR) antagonist ketamine has attracted enormous interest in mental health research owing to its rapid antidepressant actions, but its mechanism of action has remained elusive. Here we show that blockade of NMDAR-dependent bursting activity in the 'anti-reward center', the lateral habenula (LHb), mediates the rapid antidepressant actions of ketamine in rat and mouse models of depression. LHb neurons show a significant increase in burst activity and theta-band synchronization in depressive-like animals, which is reversed by ketamine. Burst-evoking photostimulation of LHb drives behavioural despair and anhedonia. Pharmacology and modelling experiments reveal that LHb bursting requires both NMDARs and low-voltage-sensitive T-type calcium channels (T-VSCCs). Furthermore, local blockade of NMDAR or T-VSCCs in the LHb is sufficient to induce rapid antidepressant effects. Our results suggest a simple model whereby ketamine quickly elevates mood by blocking NMDAR-dependent bursting activity of LHb neurons to disinhibit downstream monoaminergic reward centres, and provide a framework for developing new rapid-acting antidepressants.
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            The neuropsychopharmacology of fronto-executive function: monoaminergic modulation.

            We review the modulatory effects of the catecholamine neurotransmitters noradrenaline and dopamine on prefrontal cortical function. The effects of pharmacologic manipulations of these systems, sometimes in comparison with the indoleamine serotonin (5-HT), on performance on a variety of tasks that tap working memory, attentional-set formation and shifting, reversal learning, and response inhibition are compared in rodents, nonhuman primates, and humans using, in a behavioral context, several techniques ranging from microiontophoresis and single-cell electrophysiological recording to pharmacologic functional magnetic resonance imaging. Dissociable effects of drugs and neurotoxins affecting these monoamine systems suggest new ways of conceptualizing state-dependent fronto-executive functions, with implications for understanding the molecular genetic basis of mental illness and its treatment.
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              Astroglial Kir4.1 in the lateral habenula drives neuronal bursts in depression

              Enhanced bursting activity of neurons in the lateral habenula (LHb) is essential in driving depression-like behaviours, but the cause of this increase has been unknown. Here, using a high-throughput quantitative proteomic screen, we show that an astroglial potassium channel (Kir4.1) is upregulated in the LHb in rat models of depression. Kir4.1 in the LHb shows a distinct pattern of expression on astrocytic membrane processes that wrap tightly around the neuronal soma. Electrophysiology and modelling data show that the level of Kir4.1 on astrocytes tightly regulates the degree of membrane hyperpolarization and the amount of bursting activity of LHb neurons. Astrocyte-specific gain and loss of Kir4.1 in the LHb bidirectionally regulates neuronal bursting and depression-like symptoms. Together, these results show that a glia-neuron interaction at the perisomatic space of LHb is involved in setting the neuronal firing mode in models of a major psychiatric disease. Kir4.1 in the LHb might have potential as a target for treating clinical depression.
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                Author and article information

                Contributors
                Journal
                Neural Plast
                Neural Plast
                NP
                Neural Plasticity
                Hindawi
                2090-5904
                1687-5443
                2018
                3 May 2018
                : 2018
                : 6589608
                Affiliations
                1Department of Psychology, Jiangsu University Medical School, Zhenjiang 212013, China
                2School of Life Science, Nanjing University of Chinese Medicine, Nanjing 210023, China
                3Department of Neurosurgery, Baylor Scott & White Health, Temple, TX 76358, USA
                4Department of Surgery, College of Medicine, Texas A&M University, Temple, TX 76354, USA
                5Department of Pharmaceutical Sciences, College of Pharmacy, Texas A&M University, College Station, TX 77843, USA
                6School of Psychology, Nanjing Forest Police College, Nanjing 210023, China
                Author notes

                Academic Editor: Fang Pan

                Author information
                http://orcid.org/0000-0002-7018-8075
                http://orcid.org/0000-0001-7929-6331
                Article
                10.1155/2018/6589608
                5960543
                29853846
                c83897cf-20b7-4d1e-9dc7-da7bcac4afd5
                Copyright © 2018 Simeng Gu et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 29 December 2017
                : 2 February 2018
                : 26 March 2018
                Funding
                Funded by: Scott & White Plummer Foundation
                Funded by: National Science Foundation in China
                Award ID: 816280007
                Funded by: Jiangsu Specially Appointed Professorship Foundation
                Funded by: Jiangsu Nature Foundation
                Award ID: BK20151565
                Funded by: Jiangsu Traditional Chinese Medicine Foundation
                Award ID: ZD201351
                Funded by: Jiangsu Six Talent Peak
                Award ID: 2015YY006
                Funded by: Jiangsu Higher Education Institute
                Categories
                Research Article

                Neurosciences
                Neurosciences

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