title: Behavioural studies with a newly developed neuroprotective KYNA-amide.
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.
authors.affiliation: Department of Physiology, Anatomy and Neuroscience, University of Szeged, Közép fasor 52, Szeged, 6726, Hungary.
authors.forename: Levente
authors.initials: L
authors.lastname: Gellért
authors.forename: Dániel
authors.initials: D
authors.lastname: Varga
authors.forename: Marian
authors.initials: M
authors.lastname: Ruszka
authors.forename: József
authors.initials: J
authors.lastname: Toldi
authors.forename: Tamás
authors.initials: T
authors.lastname: Farkas
authors.forename: István
authors.initials: I
authors.lastname: Szatmári
authors.forename: Ferenc
authors.initials: F
authors.lastname: Fülöp
authors.forename: László
authors.initials: L
authors.lastname: Vécsei
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Kis
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D007736:Kynurenic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000577:Amides; D018696:Neuroprotective Agents; D007736:Kynurenic Acid