The effects of systemic theophylline administration on spike-wave discharge (SWD) frequency in genetically absence epileptic Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats are investigated. After an hour of baseline recording, animals were injected intraperitoneally (ip) with 5: 10, and 20 mg/kg theophylline and electroencephalograms (EEGs) were recorded for 2h postinjection. Then, the number and total duration of SWDs were analyzed. Spontaneous behaviors of the animals was also observed before and after drug administration. Our results show that systemic administration of theophylline suppresses the occurrence of SWDs in a dose-dependent manner. The greatest suppression was seen in the group administered 20mg/kg theophylline. Theophylline also induced a mild increase in exploratory and automatic behavior. These results indicate that blockage of adenosinergic receptors via the methylxanthine derivative theophylline decreases the occurrence of SWDs, probably by augmenting the efficacy of excitator neurotransmission and increasing vigilance and arousal levels. (C) 2004 Elsevier Inc. All rights reserved.