A novel heterocyclic compound improves working memory in the radial arm maze and modulates the dopamine receptor D1R in frontal cortex of the Sprague-Dawley rat / Hussein A.M., Aher Y.D., Kalaba P., Aher N.Y., Dragačević V., Radoman B., Ilić M., Leban J., Beryozkina T., Ahmed A.B.M.A., Urban E., Langer T., Lubec G. // Behavioural Brain Research. - 2017. - V. 332, l. . - P. 308-315.

ISSN:
01664328
Type:
Article
Abstract:
A series of compounds have been shown to enhance cognitive function via the dopaminergic system and indeed the search for more active and less toxic compounds is continuing. It was therefore the aim of the study to synthetise and test a novel heterocyclic compound for cognitive enhancement in a paradigm for working memory. Specific and effective dopamine re-uptake inhibition DAT (IC50 = 4,1 ± 0,8 μM) made us test this compound in a radial arm maze (RAM) in the rat. CE-125 (4-((benzhydrylsulfinyl)methyl)-2-cyclopropylthiazole), was tested for dopamine (DAT), serotonin and norepinephrine re-uptake inhibition by a well-established system. The working memory index (WMI) was evaluated in male Sprague Dawley rats that were intraperitoneally injected with CE-125 (1 or 10 mg/kg body weight). In order to evaluate basic neurotoxicity, the open field, elevated plus maze, rota rod studies and the forced swim test were carried out. Frontal cortex was taken at the last day of the RAM test and dopamine receptors D1R and D2R, DAT and phosphorylated DAT protein levels were determined. On the 10th day both doses were increasing the WMI as compared to the vehicle-treated group. In both, trained and treated groups, D1R levels were significantly reduced while D2R levels were unchanged. DAT levels were comparable between all groups while phosphorylated DAT levels were increased in the trained group treated with 1 mg/kg body weight. CE-125 as a probably non-neurotoxic compound and specific reuptake inhibitor was shown to increase performance (WMI) and modulation of the dopaminergic system is proposed as a possible mechanism of action. © 2017
Author keywords:
4-((Benzhydrylsulfinyl)methyl)-2-cyclopropylthiazole; Dopamine reuptake inhibition; Radial arm maze; Sprague-Dawley rat; Working memory
Index keywords:
нет данных
DOI:
10.1016/j.bbr.2017.06.023
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https://www.scopus.com/inward/record.uri?eid=2-s2.0-85021062234&doi=10.1016%2fj.bbr.2017.06.023&partnerID=40&md5=ee03d01a9e7c641da4acd344cbebdd06
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Link https://www.scopus.com/inward/record.uri?eid=2-s2.0-85021062234&doi=10.1016%2fj.bbr.2017.06.023&partnerID=40&md5=ee03d01a9e7c641da4acd344cbebdd06
Affiliations Department of Pharmaceutical Chemistry, University of Vienna, Vienna, Austria; TOS Department, Ural Federal University Named after the First President of Russia B.N. Yeltsin, 19 Mira Str., Yekaterinburg, Russian Federation; Zoology Department, Faculty of Science, Al Azhar University, Assiut, Egypt; Neuroproteomics Laboratory, Science Park, Ilkovicova 8, Bratislava, Slovakia
Author Keywords 4-((Benzhydrylsulfinyl)methyl)-2-cyclopropylthiazole; Dopamine reuptake inhibition; Radial arm maze; Sprague-Dawley rat; Working memory
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Correspondence Address Lubec, G.; Neuroproteomics Laboratory, Science Park, Ilkovicova 8, Slovakia; email: gert.lubec@lubeclab.com
Publisher Elsevier B.V.
CODEN BBRED
Language of Original Document English
Abbreviated Source Title Behav. Brain Res.
Source Scopus