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Adenosine A1 Receptor Agonist 2-chloro-N6-cyclopentyladenosine and Hippocampal Excitability During Brain Development in Rats
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SYSNO ASEP 0506568 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Adenosine A1 Receptor Agonist 2-chloro-N6-cyclopentyladenosine and Hippocampal Excitability During Brain Development in Rats Author(s) Fábera, Petr (FGU-C) ORCID
Pařízková, Martina (FGU-C)
Uttl, Libor (FGU-C) ORCID
Vondráková, Kateřina (FGU-C) RID, ORCID, SAI
Kubová, Hana (FGU-C) RID, ORCID
Tsenov, Grygoriy (FGU-C) RID, ORCID
Mareš, Pavel (FGU-C) RID, ORCIDArticle number 656 Source Title Frontiers in Pharmacology. - : Frontiers Media - ISSN 1663-9812
Roč. 10, Jun 14 (2019)Number of pages 11 s. Language eng - English Country CH - Switzerland Keywords adenosine receptor ; agonist ; development ; hippocampus ; epileptic afterdischarges ; rat Subject RIV FH - Neurology OECD category Neurosciences (including psychophysiology Method of publishing Open access Institutional support FGU-C - RVO:67985823 UT WOS 000471883300001 EID SCOPUS 85069220302 DOI 10.3389/fphar.2019.00656 Annotation Objective: The adenosinergic system may influence excitability in the brain. Endogenous and exogenous adenosine has anticonvulsant activity presumably by activating A1 receptors. Adenosine A1 receptor agonist 2-chloro-N6-cyclopentyladenosine (CCPA) may thus bolster anticonvulsant effects, but its action and the number of A1 receptors at different developmental stages are not known.
Methods: Hippocampal epileptic afterdischarges (ADs) were elicited in 12-, 15-, 18-, 25-, 45-, and 60-day-old rats. Stimulation and recording electrodes were implanted into the dorsal hippocampus. The A1 receptor agonist 2-chloro-N6-cyclopentyladenosine (CCPA, 0.5 or 1 mg/kg) was administered intraperitoneally 10 min before the first stimulation. Control animals were injected with saline. All rats were stimulated with a 2-s series of 1-ms biphasic pulses delivered at 60 Hz with increasing stepwise intensity (0.05-0.6 mA). Each age and dose group contained 9-14 animals. The AD thresholds and durations were evaluated, and the A1 receptors were detected in the hippocampus in 7-, 10-, 12-, 15-, 18-, 21-, 25-, 32-, and 52-day-old rats.
Results: Both CCPA doses significantly increased hippocampal AD thresholds in 12-, 15-, 18-, and 60-day-old rats compared to controls. In contrast, the higher dose significantly decreased AD threshold in the 25-day-old rats. The AD durations were significantly shortened in all age groups except for 25-day-old rats where they were significantly prolonged. A1 receptor expression in the hippocampus was highest in 10-day-old rats and subsequently decreased.
Significance: The adenosine A1 receptor agonist CCPA exhibited anticonvulsant activity at all developmental stages studied here except for 25-day-old rats. Age-related differences might be due to the development of presynaptic A1 receptors in the hippocampus.Workplace Institute of Physiology Contact Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Year of Publishing 2020 Electronic address https://doi.org/10.3389/fphar.2019.00656
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