当前位置： SCI文献检索 > PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY期刊下所有文献 > S 47445 counteracts the behavioral manifestations and hippocampal neuroplasticity changes in bulbectomized mice.

S 47445 counteracts the behavioral manifestations and hippocampal neuroplasticity changes in bulbectomized mice.

Abstract：

:S 47445 is a positive allosteric modulator of glutamate AMPA-type receptors that possesses procognitive, neurotrophic and enhancing synaptic plasticity properties. Its chronic administration promotes antidepressant- and anxiolytic-like effects in different rodent models of depression. We have evaluated the behavioral effects of S 47445 in the bilateral olfactory bulbectomy mice model (OB) and the adaptive changes in those proteins associated to brain neuroplasticity (BDNF and mTOR pathway). Following OB surgery, adult C57BL/6J male mice were chronically administered S 47445 (1, 3 and 10 mg/kg/day; i.p.) and fluoxetine (18 mg/kg/day; i.p.), and then behaviorally tested in the open field test. Afterwards, the expression levels of BDNF, mTOR, phospho-mTOR, 4EBP1 and phospho-4EBP1 were evaluated in hippocampus and prefrontal cortex. Both drugs reduced the OB-induced locomotor activity, a predictive outcome of antidepressant efficacy, with a similar temporal pattern of action. S 47445, but not fluoxetine, showed an anxiolytic effect as reflected by an increased central activity. Chronic administration of S 47445 reversed OB-induced changes in BDNF and phopho-mTOR expression in hippocampus but not in prefrontal cortex. The chronic administration of S 47445 induced antidepressant- and anxiolytic-like effects at low-medium doses (1 and 3 mg/kg/day, i.p.) associated with the reversal of OB-induced changes in hippocampal BDNF and mTOR signaling pathways.

journal_name

Prog Neuropsychopharmacol Biol Psychiatry

journal_title

Progress in neuro-psychopharmacology & biological psychiatry

authors

Pilar-Cuellar F,Castro E,Bretin S,Mocaer E,Pazos Á,Díaz Á

doi

10.1016/j.pnpbp.2019.04.005

subject

Has Abstract

pub_date

2019-07-13 00:00:00

pages

205-213

eissn

0278-5846

issn

1878-4216

pii

S0278-5846(18)30948-5

journal_volume

93

pub_type

杂志文章

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