The group II mGlu receptor antagonist LY341495 induces a rapid antidepressant-like effect and enhances the effect of ketamine in the chronic unpredictable mild stress model of depression in C57BL/6J mice

Pałucha-Poniewiera, Agnieszka; Podkowa, Karolina; Rafało-Ulińska, Anna

doi:10.1016/j.pnpbp.2020.110239

Cited by 33 publications

(20 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For several decades, ketamine, a non-specific antagonist of NMDARs with analgesic and anaesthetic use in high doses, has been used in the clinic, especially in veterinary medicine. The properties of metabotropic receptors also suggest their beneficial regulatory potential for the stress response, but they are not currently being fully utilised [47][48][49][50]. In the present study, an mGluR antagonist was used to determine the role of mGluRs during exposure to a single stress factor.…”

Section: Discussionmentioning

confidence: 99%

Glutamic Acid Decarboxylase Concentration Changes in Response to Stress and Altered Availability of Glutamic Acid in Rabbit (Oryctolagus cuniculus) Brain Limbic Structures

Szpręgiel

Wrońska

Kmiecik

et al. 2021

Animals

View full text Add to dashboard Cite

Glutamic acid decarboxylase (GAD) is an enzyme that catalyses the formation of γ-aminobutyric acid (GABA), the most important inhibitory neurotransmitter, from glutamic acid (Glu), which is considered the most important excitatory transmitter in the central and peripheral nervous systems. GAD is a key enzyme that provides a balance between Glu and GABA concentration. Hence, it can be assumed that if the GAD executes the synthesis of GABA from Glu, it is important in the stress response, and thus also in triggering the emotional states of the body that accompany stress. The aim of the study was to investigate the concentration of the GAD in motivational structures in the brain of the rabbit (Oryctolagus cuniculus) under altered homeostatic conditions caused by stress and variable availability of Glu. Summarising, the experimental results clearly showed variable concentrations of GAD in the motivational structures of the rabbit brain. The highest concentration of GAD was found in the hypothalamus, which suggests a strong effect of Glu and GABA on the activity of this brain structure. The GAD concentrations in individual experimental groups depended to a greater extent on blocking the activity of glutamate receptors than on the effects of a single stress exposure. The results obtained clearly support the possibility that a rapid change in the concentration of GAD could shift bodily responses to quickly achieve homeostasis, especially in this species. Further studies are necessary to reveal the role of the Glu–GAD–GABA system in the modulation of stress situations as well as in body homeostasis.

show abstract

Section: Discussionmentioning

confidence: 99%

Glutamic Acid Decarboxylase Concentration Changes in Response to Stress and Altered Availability of Glutamic Acid in Rabbit (Oryctolagus cuniculus) Brain Limbic Structures

Szpręgiel

Wrońska

Kmiecik

et al. 2021

Animals

View full text Add to dashboard Cite

show abstract

“…The NOR test is used to evaluate short-term memory in mice ( Pałucha-Poniewiera et al, 2021 ). First, a mouse was placed in a 25 cm × 25 cm × 35 cm box to adapt to 5 min.…”

Section: Methodsmentioning

confidence: 99%

Conditional Knockout of Pdha1 in Mouse Hippocampus Impairs Cognitive Function: The Possible Involvement of Lactate

et al. 2021

View full text Add to dashboard Cite

Background and Purpose: Neurodegenerative diseases are associated with metabolic disturbances. Pyruvate dehydrogenase E1 component subunit alpha (PDHA1) is an essential component in the process of glucose metabolism, and its deficiency exists in various diseases such as Alzheimer’s disease (AD), epilepsy, Leigh’s syndrome, and diabetes-associated cognitive decline. However, the exact role of PDHA1 deficiency in neurodegenerative diseases remains to be elucidated. In this study, we explored the effect of PDHA1 deficiency on cognitive function and its molecular mechanism.Methods: A hippocampus-specific Pdha1 knockout (Pdha1–/–) mouse model was established, and behavioral tests were used to evaluate the cognitive function of mice. Transmission electron microscopy (TEM) was performed to observe the morphological changes of the hippocampus. The lactate level in the hippocampus was measured. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting were used to explore the possible mechanism of the effect of PDHA1 on cognition.Results:Pdha1 knockout damaged the spatial memory of mice and led to the ultrastructural disorder of hippocampal neurons. Lactate accumulation and abnormal lactate transport occurred in Pdha1–/– mice, and the cyclic AMP-protein kinase A-cAMP response element-binding protein (cAMP/PKA/CREB) pathway was inhibited.Conclusion: Lactate accumulation caused by PDHA1 deficiency in the hippocampus may impair cognitive function by inhibiting the cAMP/PKA/CREB pathway.

show abstract

“…mGluR2/3 is elevated in animal models of chronic stress with neuronal damage in the hippocampus, suggesting that the mGluR2/3 pathway promoted neuronal damage and neuron viability [179]. Reducing the activity of mGluR2/3 using negative allosteric modulators [180] or mGluR2/3 antagonists, LY341495 [181] and LY3020371 [182] produced antidepressant effects in mice. Interestingly, the combination of (2R,6R)-HNK, a ketamine metabolite, with LY341495 elicited the same antidepressant effect as ketamine with reduced adverse effects [183].…”

Section: Metabotropic Glutamate Receptorsmentioning

confidence: 99%

Novel Pharmacological Approaches to the Treatment of Depression

Elias

Zhang

Manners

2022

Life

View full text Add to dashboard Cite

Major depressive disorder is one of the most prevalent mental health disorders. Monoamine-based antidepressants were the first drugs developed to treat major depressive disorder. More recently, ketamine and other analogues were introduced as fast-acting antidepressants. Unfortunately, currently available therapeutics are inadequate; lack of efficacy, adverse effects, and risks leave patients with limited treatment options. Efforts are now focused on understanding the etiology of depression and identifying novel targets for pharmacological treatment. In this review, we discuss promising novel pharmacological targets for the treatment of major depressive disorder. Targeting receptors including N-methyl-D-aspartate receptors, peroxisome proliferator-activated receptors, G-protein-coupled receptor 39, metabotropic glutamate receptors, galanin and opioid receptors has potential antidepressant effects. Compounds targeting biological processes: inflammation, the hypothalamic-pituitary-adrenal axis, the cholesterol biosynthesis pathway, and gut microbiota have also shown therapeutic potential. Additionally, natural products including plants, herbs, and fatty acids improved depressive symptoms and behaviors. In this review, a brief history of clinically available antidepressants will be provided, with a primary focus on novel pharmaceutical approaches with promising antidepressant effects in preclinical and clinical studies.

show abstract

The group II mGlu receptor antagonist LY341495 induces a rapid antidepressant-like effect and enhances the effect of ketamine in the chronic unpredictable mild stress model of depression in C57BL/6J mice

Cited by 33 publications

References 49 publications

Glutamic Acid Decarboxylase Concentration Changes in Response to Stress and Altered Availability of Glutamic Acid in Rabbit (Oryctolagus cuniculus) Brain Limbic Structures

Glutamic Acid Decarboxylase Concentration Changes in Response to Stress and Altered Availability of Glutamic Acid in Rabbit (Oryctolagus cuniculus) Brain Limbic Structures

Conditional Knockout of Pdha1 in Mouse Hippocampus Impairs Cognitive Function: The Possible Involvement of Lactate

Novel Pharmacological Approaches to the Treatment of Depression

Contact Info

Product

Resources

About