Abstract
The neuroactive properties and neuroprotective potential of endogenous l-kynurenine, kynurenic acid (KYNA) and its derivatives are well established. KYNA acts as an antagonist on the obligatory co-agonist glycine site, and has long been at the focus of neuroprotective trials. Unfortunately, KYNA is barely able to cross the blood–brain barrier. Accordingly, the development and synthesis of KYNA analogs which can readily cross the BBB have been at the focus of research interest with the aim of neuroprotection. Earlier we reported a new KYNA-amide crosses the BBB and proved neuroprotective in several experiments. In the present study, we investigated the locomotor activity, working memory performance, and also the long-lasting, consolidated reference memory of animals treated intraperitoneally (i.p.) with the novel analog. The effects of the novel analog on the spatial orientation and learning ability of rats were assessed in the Morris water maze (MWM) paradigm. The effects on locomotor activity of mice was assessed in the open field (OF) paradigm, and those on the spatial orientation and learning ability of mice were investigated in the radial arm maze (RAM) paradigm. It emerged that there is a dose of this KYNA-amide which is neuroprotective, but does not worsen the cognitive function of the brain. This result is significant in that a putative neuroprotectant without adverse cognitive side-effects is of great benefit.
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Acknowledgments
The present study was supported by grants from OTKA (K 75628), TÁMOP-4.2.1/B-09/1/KONV-2010-0005, ETT(02-64), and the Teller Ede Foundation (NAP-BIO-06-BAYBIOSZ). T.F. is a Bolyai Fellow of the Hungarian Academy of Sciences. Thanks are due to Szabolcs Oláh for his useful advice in the course of the statistical analysis.
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Gellért, L., Varga, D., Ruszka, M. et al. Behavioural studies with a newly developed neuroprotective KYNA-amide. J Neural Transm 119, 165–172 (2012). https://doi.org/10.1007/s00702-011-0692-8
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DOI: https://doi.org/10.1007/s00702-011-0692-8