Abstracts

Rationale: Caffeine is widely used excitatory drug with possible negative effect on epileptic activities. We analyzed possible participation of caffeine in immediate postictal changes in excitability in immature rats.

Methods: Two age groups were studied: 12- and 25-day-old rats. Flat cortical epidural electrodes were implanted under inhalation anesthesia – two for stimulation over right sensorimotor area and four for registration. Indifferent and grounding electrodes were placed over cerebellum. Epileptic afterdischarges (ADs) were elicited by 15-s series of 8-Hz stimulation with suprathreshold intensity. Presence or absence of ADs, their duration and accompanying motor phenomena. Two series of twin stimulation were applied with a 1-min time between the ADs, then drug was administered and after 10 min the second two stimulations were applied. Not only caffeine (doses of 10 and 20 mg/kg) but also an A1 receptor antagonist DPCPX (1 mg/kg i.p.) and A2 receptor agonist CGS 21680 (1 mg/kg i.p.) were administered. Caffeine was dissolved in physiological saline, the other two drugs in 50% DMSO.

Results: The first AD was taken as conditioning one, the second AD as the testing one. Control pairs exhibited prolongation of the testing response in 12-day-old rats. Caffeine in the 10-mg/kg dose markedly prolonged the first (conditioning) AD, bur the second (testing) AD was shorter than the conditioning one. The older group exhibited typical postictal depression the testing AD (if present) was significantly shorter than the conditioning one. Neither dose of caffeine change the duration of the conditioning response, the testing AD was significantly longer than in the predrug pair. DPCPX demonstrated  lengthening of the conditioning AD but shortening of the testing AD in the younger group in comparison with predrug controls. The 25-day-old animals exhibited prolongation of conditioning ADs after DPCPX and a tendency to longer testing ADs if compared with controls. CGS 21680 led to significant prolongation of the conditioning AD in 12-day-old rats and only a tendency to longer duration of ADs in the older group.

Conclusions: Caffeine and A1 receptor antagonist DPCPX markedly prolonged conditioning ADs in 12-day-old group and increased the duration of testing ADs in 25-dy-old rats. No marked effects of A2A receptor agonist CGS 21680 were found demonstrating the primary role of A1 receptors in caffeine effects on postseizure excitability.

Funding: This study was supported by project PHARMABRAIN, reg. no. CZ.02.1.01/0.0/0.0/16_025/0007444 (co-supported by EU) and Research Project RVO 67985823.