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Antidepressant-like activity of the neuropeptide Y Y5 receptor antagonist Lu AA33810: behavioral, molecular, and immunohistochemical evidence

Content Provider	Springer Nature Link
Author	Domin, Helena Szewczyk, Bernadeta Pochwat, Bartłomiej Woźniak, Monika Śmiałowska, Maria
Copyright Year	2016
Abstract	It 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.In 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.We 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.Our results indicate that Lu AA33810 exerts an antidepressant-like effect and suggest the Y5 receptors as a promising target for antidepressant therapy.
Starting Page	631
Ending Page	645
Page Count	15
File Format	PDF
ISSN	00333158
Journal	Psychopharmacology
Volume Number	234
Issue Number	4
e-ISSN	14322072
Language	English
Publisher	Springer Berlin Heidelberg
Publisher Date	2016-12-14
Publisher Place	Berlin, Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Astrocyte Antidepressant BDNF Lu AA33810 GFAP Neuropeptide Y Prefrontal cortex Gliotoxin Forced swim test Neurosciences Pharmacology/Toxicology Psychiatry
Content Type	Text
Resource Type	Article
Subject	Pharmacology

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Antidepressant-like activity of the neuropeptide Y Y5 receptor antagonist Lu AA33810: behavioral, molecular, and immunohistochemical evidence

The Novel Neuropeptide Y Y5 Receptor Antagonist Lu AA33810 [N-[[trans-4-[(4,5-Dihydro[1]benzothiepino[5,4- d]thiazol-2-yl)amino]cyclohexyl]methyl]-methanesulfonamide] Exerts Anxiolytic- and Antidepressant-Like Effects in Rat Models of Stress Sensitivity (2008)

Ethanol induced antidepressant-like effect in the mouse forced swimming test: modulation by serotonergic system

The novel neuropeptide Y Y5 receptor antagonist Lu AA33810 [N-[[trans-4-[(4,5-dihydro[1]benzothiepino[5,4-d]thiazol-2-yl)amino]cyclohexyl]methyl]-methanesulfonamide] exerts anxiolytic- and antidepressant-like effects in rat models of stress sensitivity.

Activation of the trkb neurotrophin receptor is induced by antidepressant drugs and is required for antidepressant-induced behavioral effects (2003).

Activation of the nmda/glutamate receptor.

Combined gene overexpression of neuropeptide Y and its receptor Y5 in the hippocampus suppresses seizures

Antidepressant-Like Activity of Typical Antidepressant Drugs in the Forced Swim Test and Tail Suspension Test in Mice Is Augmented by DMPX, an Adenosine A_2A Receptor Antagonist.

Group II mGlu receptor antagonist LY341495 enhances the antidepressant-like effects of ketamine in the forced swim test in rats

Antidepressant-like activity of the neuropeptide Y Y5 receptor antagonist Lu AA33810: behavioral, molecular, and immunohistochemical evidence

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Antidepressant-like activity of the neuropeptide Y Y5 receptor antagonist Lu AA33810: behavioral, molecular, and immunohistochemical evidence

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Activation of the trkb neurotrophin receptor is induced by antidepressant drugs and is required for antidepressant-induced behavioral effects (2003).

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