Intrahippocampal administration of 5-HT6 receptor drugs on memory consolidation and amnesia protocols

Aparicio-Nava, L.; Tellez, Ruth; González, Roberto; Liy-Salmerón, Gustavo; Meneses, Alfredo

doi:10.1016/j.bbr.2018.11.021

Cited by 9 publications

(6 citation statements)

References 64 publications

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“…The injection of 5-HT 6 agonists such as EMD-386088, EMDT and WAY-208466 in different doses and routes of administration induces procognitive actions in models such as MWM, passive avoidance task, autoshaping memory task and NORT. Putatively, the effects of these drugs may be related to the increase in several molecules at the hippocampus including cAMP response element-binding, brain-derived neurotrophic factor, dopamine, glutamate, gamma-aminobutyric acid and acetylcholine, phospho-Thr (202/204)-Erk1/2, c-fos and Arc (Pereira et al, 2015;Jastrzębska et al, 2018;Aparicio-Nava et al, 2019). Surprisingly, the 5-HT 6 R antagonists SB-258585, SB-399885 and SUVN-502 also exert procognitive effects in the NORT, the MWM and the radial maze through different mechanisms of action.…”

Section: Discussionmentioning

confidence: 99%

The 5-HT6R agonist E-6837 and the antagonist SB-271046 reverse the psychotic-like behaviors induced by ketamine

Suárez-Santiago

Roldán

Picazo

2022

Behavioural Pharmacology

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Schizophrenia is a serious mental disorder that affects 1% of the world's population. Although various therapeutic tools have been developed since the appearance of the first generation of antipsychotics, the effect of these agents does not manage to attenuate a significant part of psychotic symptoms. Ketamine is an anesthetic agent able to produce psychotic-like symptoms through the antagonism of the glutamatergic N-methyl-d-aspartic acid (NMDA) receptors (NMDARs). This drug has been widely used to study new pharmacological tools with potential antipsychotic properties. On the contrary, it is known that the 5-HT 6 receptor agonist and antagonist drugs induce procognitive, anxiolytic and antidepressant effects in different preclinical models. Therefore, the aim of this study was to evaluate the behavioral actions of the 5-HT 6 receptors' agonist E-6837 and the antagonist SB-271046, in ICR-CD1 mice previously treated with a subchronic ketamine scheme (10 mg/kg i.p. daily for 5 days). Results showed that repeated administration of ketamine induced recognition memory deficit, anxiogenic effects, obsessivecompulsive behaviors and stereotyped movements. The acute administration of both 5-HT 6 agents reversed the memory deficit and induced a decrease in anxiety, whereas SB-271046 administration produced a decrease in climbing behavior. The injection of either of these 5-HT 6 drugs had no effect in the light-dark test. Surprisingly, when these drugs were injected together with ketamine, anxiogenic actions were produced. Current findings suggest that both agonist and antagonist 5-HT 6 drugs play an important role in modulating psychoticlike symptoms induced by the subchronic blockade of NMDAR.

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Section: Discussionmentioning

confidence: 99%

The 5-HT6R agonist E-6837 and the antagonist SB-271046 reverse the psychotic-like behaviors induced by ketamine

Suárez-Santiago

Roldán

Picazo

2022

Behavioural Pharmacology

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“…At present, a lot of knowledge about memory comes from the study of memory impairment, especially amnesia. [35][36][37]. Other neurological diseases, such as Alzheimer's disease [38], Parkinson's disease [39,40] and Korsakoff's syndrome [41] also accompany with impaired memory.…”

Section: Discussionmentioning

confidence: 99%

Astragaloside IV enhances memory and modulates hippocampal synaptic plasticity by decreasing GABAergic inhibition through EGR-1 mediated BDNF/TrkB signaling pathway in mice

Huang

Lan

Zhou

et al. 2020

Preprint

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Background Astragaloside IV (ASIV) is one of the saponins isolated from Astragalus membranaceus, a widely used traditional Chinese medicine and a health product sold all over the world. However, so far, the effect of ASIV on GABAergic synaptic transmission has not been elucidated yet. In the present study, the effect of ASIV on memory and hippocampal synaptic plasticity was investigated in mice and down-regulated early growth response protein 1 (EGR-1) knockout mice. Methods Behavior tests including radial-arm maze test and shuttle-box test, liquid chromatography-tandem mass spectrometry, western blotting analysis, quantitative PCR, electrophysiological recording, and electron microscopy were used in this study. The difference of data was detected by unpaired student t-test or two-factor analysis of variance (ANOVA) or Mann-Whitney U test. Results ASIV was shown to enhance the learning and memory of mice in behavior tests, such as radial-arm maze test and shuttle-box test, as well as the synaptic plasticity in electrophysiological experiments. Moreover, it significantly reduced the concentration of gamma-aminobutyric acid (GABA) and the expression of glutamate decarboxylase 2 (GAD65) in mouse hippocampus, which was accompanied with decreased ratio of inhibitory synapses, and EGR-1, brain-derived neurotrophic factor (BDNF) and tyrosine receptor kinase B (TrkB). When EGR-1 was knocked out, the promotive effects of ASIV on memory and synaptic plasticity, as well as the inhibitory effects on GAD65, BDNF and TrkB, were abolished. In addition, ASIV was found to down-regulate the pre-existing EGR-1 baseline to better adapt to the learning stimuli. Conclusions Together, these results demonstrated a novel role of ASIV in enhancing memory and modulating hippocampal synaptic plasticity by decreasing GABAergic inhibition through EGR-1 mediated BDNF/TrkB signaling pathway in mice.

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“…This is partly due to the information is assumed to be transiently stored in short-term memory while it is considered to integrate long-term memory permanently [38]. At present, a lot of knowledge about memory comes from the study of memory impairment, especially amnesia [39][40][41]. Other neurological diseases, such as Alzheimer's disease [42], Parkinson's disease [43,44]and Korsakoff's syndrome [45] also accompany with impaired memory.…”

Section: Discussionmentioning

confidence: 99%

Astragaloside IV suppressed hippocampal GABAergic synaptic transmission and enhanced memory through EGR-1 mediated BDNF/TrkB signaling pathway in mice

Huang¹,

Xue²,

Lan³

et al. 2020

Preprint

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Background: Astragaloside IV (ASIV) is one of the saponins isolated from Astragalus membranaceus, a widely used traditional Chinese medicine and a health product sold all over the world. However, so far, the effect of ASIV on GABAergic synaptic transmission has not been elucidated yet. In the present study, the effect of ASIV on memory and hippocampal GABAergic synaptic transmission was investigated in wild type and early growth response protein 1 (EGR-1) knockout mice. Methods: Behavioral tests including radial-arm maze test and shuttle-box test, liquid chromatography-tandem mass spectrometry, western blotting analysis, quantitative PCR, electrophysiological recording, and electron microscopy were used in this study. Results: ASIV was shown to enhance the learning and memory of mice in behavioral tests, such as radial-arm maze test and shuttle-box test. It significantly reduced the concentration of GABA, the expression of glutamate decarboxylase 2 (GAD65) as well as the ratio of inhibitory synapses in mouse hippocampus, which was accompanied with a suppression of hippocampal spontaneous inhibitory postsynaptic currents. ASIV administration decreased the expression of EGR-1, brain-derived neurotrophic factor (BDNF) and tyrosine receptor kinase B (TrkB) in the hippocampus. Furthermore, blockage of BDNF/TrkB signaling with K-252a abrogated the effect of ASIV on GAD65 expression. When EGR-1 was knocked out, the promotive effects of ASIV on learning and memory, as well as the inhibitory effects on GABAergic synaptic transmission and GAD65, BDNF and TrkB expression, were abolished. In addition, ASIV was found to down-regulate the pre-existing EGR-1 baseline to better adapt to the learning stimuli. Conclusions: Together, these results demonstrated a novel role of ASIV in enhancing memory and reducing hippocampal GABAergic synaptic transmission through EGR-1 mediated BDNF/TrkB signaling pathway in mice.

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Intrahippocampal administration of 5-HT6 receptor drugs on memory consolidation and amnesia protocols

Cited by 9 publications

References 64 publications

The 5-HT6R agonist E-6837 and the antagonist SB-271046 reverse the psychotic-like behaviors induced by ketamine

The 5-HT6R agonist E-6837 and the antagonist SB-271046 reverse the psychotic-like behaviors induced by ketamine

Astragaloside IV enhances memory and modulates hippocampal synaptic plasticity by decreasing GABAergic inhibition through EGR-1 mediated BDNF/TrkB signaling pathway in mice

Astragaloside IV suppressed hippocampal GABAergic synaptic transmission and enhanced memory through EGR-1 mediated BDNF/TrkB signaling pathway in mice

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