ArticlePsychopharmacology2017
Antidepressant-like activity of the neuropeptide Y Y5 receptor antagonist Lu AA33810: behavioral, molecular, and immunohistochemical evidence.
Article in Psychopharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 23 citations in OpenAlex.
- Antidepressant Effects of 20-Glucoginsenoside Rf in an L-AAA-Induced Mouse Model with Glial-Associated Molecular Alterations.Current issues in molecular biology · 2026Article
- Sugarcane Polyphenols Improve Depressive-like Behavior in CUMS Mice by Promoting the MAPK/ERK Signaling Pathway and Inhibiting NLRP3 Inflammasome Pyroptosis.Foods (Basel, Switzerland) · 2026Article
- Antidepressant Effects of Ginsenoside Rc on L-Alpha-Aminoadipic Acid-Induced Astrocytic Ablation and Neuroinflammation in Mice.International journal of molecular sciences · 2024Article
- Antidepressant Effect ofNutrients · 2024Article
- Bridging the Mind and Gut: Uncovering the Intricacies of Neurotransmitters, Neuropeptides, and their Influence on Neuropsychiatric Disorders.Central nervous system agents in medicinal chemistry · 2024Review
- GluN2A-ERK-mTOR pathway confers a vulnerability to LPS-induced depressive-like behaviour.Behavioural brain research · 2022Article
- Update on GPCR-based targets for the development of novel antidepressants.Molecular psychiatry · 2022Review
- NLRP3/caspase-1/GSDMD-mediated pyroptosis exerts a crucial role in astrocyte pathological injury in mouse model of depression.JCI insight · 2021Article
- Article
- Antidepressant effects of ginsenoside Rf on behavioral change in the glial degeneration model of depression by reversing glial loss.Journal of ginseng research · 2020Article
- Neuropeptide Y Is an Immunomodulatory Factor: Direct and Indirect.Frontiers in immunology · 2020Review
- The ERK Pathway: Molecular Mechanisms and Treatment of Depression.Molecular neurobiology · 2019Review
- NPY Receptor 2 Mediates NPY Antidepressant Effect in the mPFC of LPS Rat by Suppressing NLRP3 Signaling Pathway.Mediators of inflammation · 2019Article
- Neuropeptide Y in Alcohol Addiction and Affective Disorders.Frontiers in endocrinology · 2017Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
rationaleIt has recently been found that chronic treatment with the highly selective, brain-penetrating Y5 receptor antagonist, Lu AA33810 [N-[[trans-4-[(4,5-dihydro [1] benzothiepino[5,4-d] thiazol-2-yl) amino] cyclohexyl]methyl]-methanesulfonamide], produces antidepressant-like effects in the rat chronic mild stress model.
objectiveIn the present study, we investigated the possible antidepressant-like activity of Lu AA33810 in rats subjected to glial ablation in the prefrontal cortex (PFC) by the gliotoxin L-AAA, which is an astroglial degeneration model of depression.
resultsWe observed that Lu AA33810 administered intraperitoneally at a single dose of 10 mg/kg both reversed depressive-like behavioral changes in the forced swim test (FST) and prevented degeneration of astrocytes in the mPFC. The mechanism of antidepressant and glioprotective effects of Lu AA33810 has not been studied, so far. We demonstrated the contribution of the noradrenergic rather than the serotonergic pathway to the antidepressant-like action of Lu AA33810 in the FST. Moreover, we found that antidepressant-like effect of Lu AA33810 was connected with the influence on brain-derived neurotrophic factor (BDNF) protein expression. We also demonstrated the antidepressant-like effect of Lu AA33810 in the FST in rats which did not receive the gliotoxin. We found that intracerebroventricular injection of the selective MAPK/ERK inhibitor U0126 (5 μg/2 μl) and the selective PI3K inhibitor LY294002 (10 nmol/2 μl) significantly inhibited the anti-immobility effect of Lu AA33810 in the FST in rats, suggesting that MAPK/ERK and PI3K signaling pathways could be involved in the antidepressant-like effect of Lu AA33810.
conclusionOur results indicate that Lu AA33810 exerts an antidepressant-like effect and suggest the Y5 receptors as a promising target for antidepressant therapy.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.