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Antidepressant-relevant behavioral and synaptic molecular effects of long-term fasudil treatment in chronically stressed male rats

dc.contributor.authorRomán-Albasini L.
dc.contributor.authorDíaz-Véliz G.
dc.contributor.authorOlave F.A.
dc.contributor.authorAguayo F.I.
dc.contributor.authorGarcía-Rojo G.
dc.contributor.authorCorrales W.A.
dc.contributor.authorSilva J.P.
dc.contributor.authorÁvalos A.M.
dc.contributor.authorRojas P.S.
dc.contributor.authorAliaga E.
dc.contributor.authorFiedler J.L.
dc.date.accessioned2020-09-02T22:27:28Z
dc.date.available2020-09-02T22:27:28Z
dc.date.issued2020
dc.identifier10.1016/j.ynstr.2020.100234
dc.identifier.citation13, , -
dc.identifier.issn23522895
dc.identifier.urihttps://hdl.handle.net/20.500.12728/6077
dc.descriptionSeveral lines of evidence suggest that antidepressant drugs may act by modulating neuroplasticity pathways in key brain areas like the hippocampus. We have reported that chronic treatment with fasudil, a Rho-associated protein kinase inhibitor, prevents both chronic stress-induced depressive-like behavior and morphological changes in CA1 area. Here, we examined the ability of fasudil to (i) prevent stress-altered behaviors, (ii) influence the levels/phosphorylation of glutamatergic receptors and (iii) modulate signaling pathways relevant to antidepressant actions. 89 adult male Sprague-Dawley rats received intraperitoneal fasudil injections (10 mg/kg/day) or saline vehicle for 18 days. Some of these animals were daily restraint-stressed from day 5–18 (2.5 h/day). 24 hr after treatments, rats were either evaluated for behavioral tests (active avoidance, anxiety-like behavior and object location) or euthanized for western blot analyses of hippocampal whole extract and synaptoneurosome-enriched fractions. We report that fasudil prevents stress-induced impairments in active avoidance, anxiety-like behavior and novel location preference, with no effect in unstressed rats. Chronic stress reduced phosphorylations of ERK-2 and CREB, and decreased levels of GluA1 and GluN2A in whole hippocampus, without any effect of fasudil. However, fasudil decreased synaptic GluA1 Ser831 phosphorylation in stressed animals. Additionally, fasudil prevented stress-decreased phosphorylation of GSK-3β at Ser9, in parallel with an activation of the mTORC1/4E-BP1 axis, both in hippocampal synaptoneurosomes, suggesting the activation of the AKT pathway. Our study provides evidence that chronic fasudil treatment prevents chronic stress-altered behaviors, which correlated with molecular modifications of antidepressant-relevant signaling pathways in hippocampal synaptoneurosomes. © 2020 The Authors
dc.language.isoen
dc.publisherElsevier Inc
dc.subjectAntidepressants
dc.subjectBehavior
dc.subjectChronic stress
dc.subjectFasudil
dc.subjectHippocampus
dc.subjectSynaptoneurosomes
dc.subjectcyclic AMP responsive element binding protein
dc.subjectfasudil
dc.subjectglutamate receptor 1
dc.subjectglutamate receptor 2
dc.subjectmitogen activated protein kinase 1
dc.subjectactive avoidance test
dc.subjectanimal cell
dc.subjectanimal experiment
dc.subjectanimal model
dc.subjectanimal tissue
dc.subjectantidepressant activity
dc.subjectanxiety
dc.subjectArticle
dc.subjectbehavior change
dc.subjectbehavior disorder
dc.subjectchronic stress
dc.subjectcontrolled study
dc.subjectelevated plus maze test
dc.subjectglutamatergic synapse
dc.subjecthippocampus
dc.subjectmale
dc.subjectnonhuman
dc.subjectphosphorylation
dc.subjectpriority journal
dc.subjectrat
dc.subjectsignal transduction
dc.subjectSprague Dawley rat
dc.subjectstatistical analysis
dc.subjectsynaptic efficacy
dc.subjectWestern blotting
dc.titleAntidepressant-relevant behavioral and synaptic molecular effects of long-term fasudil treatment in chronically stressed male rats
dc.typeArticle


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