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4型磷酸二酯酶抑制剂依他唑酯在焦虑症实验模型中的抗焦虑样作用

Anxiolytic-like effect of etazolate, a type 4 phosphodiesterase inhibitor in experimental models of anxiety.

作者信息

Ankur Jindal, Mahesh Radhakrishan, Bhatt Shvetank

机构信息

Department of Pharmacy, Birla Institute of Technology & Science, Pilani 333 031, India.

出版信息

Indian J Exp Biol. 2013 Jun;51(6):444-9.

PMID:23926692
Abstract

Etazolate is a selective inhibitor of type 4 phosphodiesterase (PDE4) class enzyme. Antidepressant-like effect of etazolate has been previously demonstrated in the rodent models of depression. The present study was designed to investigate the anxiolytic-like activity of etazolate in experimental mouse models of anxiety. The putative anxiolytic effect of etazolate (0.25-1 mg/kg, ip) was studied in mice by using a battery of behavioural tests of anxiety such as elevated plus maze (EPM), light/dark (L/D) aversion, hole board (HB) and open field (OFT) with diazepam (2 mg/kg, ip) as reference anxiolytic. Like diazepam (2 mg/kg, ip), etazolate (0.5 and 1 mg/kg, ip) significantly increased the percentage of both time spent and entries into open arms in the EPM test. In the L/D test etazolate (0.5 and 1 mg/kg, ip) increased the both total time spent in and latency time to leave the light compartment. Etazolate (0.5 and 1 mg/kg, ip) also significantly increased head dipping scores and time spent in head dipping, whereas significantly decreased the head dipping latency in HB test. In addition, etazolate (0.5 and 1 mg/kg, ip) significantly increased the ambulation scores (square crossed) and number of rearing in OFT. In conclusion, these findings indicated that etazolate exhibited an anxiolytic-like effect in experimental models of anxiety and may be considered an alternative approach for the management of anxiety disorder.

摘要

依他唑酯是一种4型磷酸二酯酶(PDE4)类酶的选择性抑制剂。依他唑酯的抗抑郁样作用先前已在抑郁症啮齿动物模型中得到证实。本研究旨在探讨依他唑酯在实验性小鼠焦虑模型中的抗焦虑样活性。以地西泮(2mg/kg,腹腔注射)作为参考抗焦虑药,通过一系列焦虑行为测试,如高架十字迷宫(EPM)、明暗(L/D)厌恶、洞板(HB)和旷场试验(OFT),研究了依他唑酯(0.25 - 1mg/kg,腹腔注射)假定的抗焦虑作用。与地西泮(2mg/kg,腹腔注射)一样,依他唑酯(0.5和1mg/kg,腹腔注射)在EPM试验中显著增加了在开放臂停留的时间百分比和进入开放臂的次数。在L/D试验中,依他唑酯(0.5和1mg/kg,腹腔注射)增加了在亮区停留的总时间和离开亮区的潜伏期。依他唑酯(0.5和1mg/kg,腹腔注射)还显著增加了HB试验中的探头得分和探头时间,而显著缩短了探头潜伏期。此外,依他唑酯(0.5和1mg/kg,腹腔注射)显著增加了OFT中的行走得分(穿过的方格数)和直立次数。总之,这些发现表明依他唑酯在实验性焦虑模型中表现出抗焦虑样作用,可能被认为是治疗焦虑症的一种替代方法。

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Etazolate, a phosphodiesterase-4 enzyme inhibitor produces antidepressant-like effects by blocking the behavioral, biochemical, neurobiological deficits and histological abnormalities in hippocampus region caused by olfactory bulbectomy.
依他唑酯是一种磷酸二酯酶-4抑制剂,它通过阻断嗅球切除引起的行为、生化、神经生物学缺陷以及海马区的组织学异常,产生抗抑郁样作用。
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