In:
Pharmacology Research & Perspectives, Wiley, Vol. 3, No. 2 ( 2015-03)
Abstract:
We characterized mice administered corticosterone ( CORT ) at a dose of 20 mg/kg for 3 weeks to determine their suitability as a model of mood disorders and found that the time immobilized in the tail suspension test was longer and the time spent in the open arms of the elevated plus‐maze test was shorter than those of the vehicle‐treated group, findings demonstrating that chronic CORT induced both depression‐like and anxiety‐like behaviors. Furthermore, the levels of phosphorylated extracellular signal‐regulated kinase ( pERK ) 1/2 in the hippocampus and cerebral cortex were reduced in the CORT ‐treated group. Using this model, we investigated the protective effect of the ester, thioester, and amide compounds of 2‐decenoic acid derivatives (termed compounds A, B, and C, respectively). The potency of the protective activity against the CORT ‐induced depression‐like or anxiety‐like behaviors and the reduction in pERK 1/2 level were found to be in the following order: compound B 〉 compound C 〉 compound A. Therefore, we further investigated the therapeutic activity of only compound B, and its effect on depression‐like behavior was observed after oral administration for 1 or 2 weeks, and its effect on anxiety‐like behavior was observed after oral administration for 3 weeks. The ratios of phosphorylated ERK 1/2, Akt, and cAMP ‐response element‐binding protein to their respective nonphosphorylated forms were smaller in the CORT ‐treated group than in the vehicle‐treated group; however, subsequent treatment with compound B at either 0.3 or 1.5 mg/kg significantly ameliorated this reduction. Compound B appeared to elicit intracellular signaling, similar to that elicited by brain‐derived neurotrophic factor, and its mode of action was shown to be novel and different from that of fluvoxamine, a currently prescribed drug for mood disorders.
Type of Medium:
Online Resource
ISSN:
2052-1707
,
2052-1707
Language:
English
Publisher:
Wiley
Publication Date:
2015
detail.hit.zdb_id:
2740389-0
SSG:
15,3
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