THIOPENTAL UNCOUPLES HIPPOCAMPAL AND CORTICAL SYNCHRONIZED ELECTROENCEPHALOGRAPHIC ACTIVITY

Background: Thiopental produces a concentration-dependent continuum of effects on the cortical electroencephalogram (EEG) that has been link ed to behavioral measures of anesthetic depth. The complexity of the r esponse, however, limits a clear insight into the neurophysiologic act ions of thiopental. The current study investigated thiopental actions on cortical EEG and hippocampal electrical activity, to determine whet her similar effects occur on both structures and to compare synchroniz ed activity between these structures. Methods: Thiopental was administ ered intravenously via an implanted catheter in freely moving rats. Ar terial blood oxygen/carbon dioxide concentration, thiopental concentra tions, and temperature were monitored and controlled, Neocortical EEG was recorded from implanted dural surface electrodes and hippocampal n euron electrical activity was recorded from stereotaxically placed mic roelectrodes. Pharmacokinetic models were used to determine effect sit e concentrations. Results: Thiopental produced an increase in EEG freq uency and amplitude at low concentrations (15-20 mu g/ml total plasma, similar to 10 mu M unbound), which produced a loss of righting reflex . This was followed by a frequency decrease and burst suppression acti vity at higher concentrations (50-80 mu g/ml, similar to 60 mu M), whi ch produced a loss of tail pinch and corneal reflexes. Higher concentr ations of thiopental (>60 mu g/ml) uncoupled synchronized burst discha rges recorded in hippocampus and cortex, Isoelectric EEG activity was associated with concentrations of 70-90 mu g/ml (similar to 80 mu M) a nd a deep level of anesthesia; motor reflexes were abolished, although cardiovascular reflexes remained. In all frequency bands, similar con centration-PEG effect relationships were observed for cortical and hip pocampal signals, only differing in the magnitude of response, A rever sed progression of effects was observed on recovery. Conclusions: The results confirm earlier findings in humans and animals and demonstrate that both the hippocampus and neocortex exhibit burst suppression and isoelectric activity during thiopental anesthesia. Thiopental-induced synchronized burst activity was depressed by progressively higher con centrations. The lost synchronization suggests a depression of synapti c coupling between cortical structures contributes to anesthesia.