Adenosine A1 Receptor Agonist 2-chloro-N6-cyclopentyladenosine and Hippocampal Excitability During Brain Development in Rats

0506568 - FGÚ 2020 RIV CH eng J - Journal Article
Fábera, Petr - Pařízková, Martina - Uttl, Libor - Vondráková, Kateřina - Kubová, Hana - Tsenov, Grygoriy - Mareš, Pavel
Adenosine A1 Receptor Agonist 2-chloro-N6-cyclopentyladenosine and Hippocampal Excitability During Brain Development in Rats.
Frontiers in Pharmacology. Roč. 10, Jun 14 (2019), č. článku 656. ISSN 1663-9812. E-ISSN 1663-9812
Institutional support: RVO:67985823
Keywords : adenosine receptor * agonist * development * hippocampus * epileptic afterdischarges * rat
OECD category: Neurosciences (including psychophysiology
Impact factor: 4.225, year: 2019
Method of publishing: Open access
https://doi.org/10.3389/fphar.2019.00656

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.
Permanent Link: http://hdl.handle.net/11104/0297800