Modifications of brain electrical activity after activation of the benzodiazepine receptor types in rats and rabbits

The present study reports a comparative electroencephalographic (EEG) study of drugs belonging to different chemical classes which share the property to bind at benzodiazepine (BDZ) recognition sites. The EEG patterns are recorded from the neocortex of rats and rabbits as well as from dorsal hippocampus and red nucleus in rabbits after intravenous administration of diazepam (0.1-10 mg/kg), clonazepam (0.02-2.5 mg/kg), zopiclone (0.3-3 mg/kg), flunitrazepam (0.03-2.5 mg/kg), CGS 9896 (0.1-3 mg/kg), zolpidem (0.1-3 mg/kg) and Cl 218,872 (0.1-10 mg/kg). The most relevant differences are observed at the level of the neocortex. All drugs induced appearance of 7-12 Hz spindle bursts. On the contrary, the presence of 15-30 Hz waves (defined beta-like activity) mainly occurs after diazepam, clonazepam and zopiclone. Scarce beta-like activity is present after CGS 9896, zolpidem and Cl 218,872. According to the selectivity of these drugs for the various types of BDZ receptor, one can speculate that activation of BDZ2 is relevant for the appearance of the beta-like activity. Flunitrazepam, diazepam, and zolpidem increase the amplitude of the red nucleus waves. Such an effect is less marked after zopiclone and CGS 9896, whereas is almost absent after clonazepam and Cl 218,872. A reduction of the frequency is observed after flunitrazepam, diazepam, clonazepam, CGS 9896 and zolpidem, whereas it is almost absent after zopiclone and Cl 218,872. Finally, all drugs induce a reduction of the amplitude of the hippocampal theta rhythms, whereas after diazepam, flunitrazepam, zolpidem and CGS 9896 a slowing of the record also occurs.