An EEG and behavioural study on the excitatory properties of caffeine in rabbits

In the present work we have investigated some of the excitatory effects of caffeine in rabbits. Caffeine (5-50 mg/kg i.v.) elicited a cortical EEG desynchronization and an activation of the theta hippocampal rhythm but failed to affect the red nucleus activity. The EEG effects of caffeine were counteracted by L-PIA (1-3 mg/kg i.v.). Caffeine (25-50 mg/kg i.v.) completely reverted the EEG and motor effects due to L-PIA (1-5 mg/kg); the drug also counteracted the cortical and hippocampal EEG modifications elicited by diazepam (1-10 mg/kg), but failed to influence the diazepam-induced effects at the red nucleus level. In addition, caffeine (25 mg/kg) significantly increased the duration of the epileptiform EEG response (afterdischarge) elicited by electrical stimulation of the dorsal hippocampus. This caffeine-potentiating effect was reduced by administration of both L-PIA (0.05-2 mg/kg) and diazepam (1 mg/kg); Ro 15-1788 (1 mg/kg) was unable to affect it. Present data suggest that the analeptic action of caffeine is different from that of the drugs acting through the GABA-benzodiazepine system. Our results show the importance of the limbic system in the excitatory effects of caffeine and suggest that purinergic drugs may have a modulatory role in the control of limbic convulsions.