Differential effects of phenobarbital and pentobarbital on stimulus train-induced bursting in the hippocampal slice

Stimulus train-induced bursting (STIB) in the hippocampal slice is an in vitro model of epileptiform activity that is analogous to kindling and requires no manipulation of the neurochemical or ionic environment. The bursts recorded from slices after STIB closely resemble the discharges observed in vivo after kindling and may provide a convenient and accessible model for studies of the electrophysiological underpinnings of epileptiform bursting in local neural circuits. One critical element in the validation of this model is the responsiveness of STIB to traditional sedatives and anticonvulsants. In this study we assessed the effects of the barbiturates phenobarbital and pentobarbital on both spontaneous and stimulus-triggered bursts after STIB. Concentration-response studies indicated that both drugs had inhibitory effects on stimulus-triggered bursting, although at significantly different concentrations. The rate of spontaneous bursting, however, was not significantly affected by phenobarbital at any of the concentrations tested, whereas pentobarbital reduced the frequency of spontaneous bursting in a concentration-dependent manner. These results indicate that STIB is responsive to the barbiturates tested, although the drugs have differential potencies depending on the type of bursting measured. These effects may be the result of differential potencies of these drugs on gamma-aminobutyric acid-mediated inhibition within local hippocampal circuits, as well as different effects on the biophysical characteristics of pacemaker cells within these circuits.