Dithiothreitol elicits epileptiform activity in CA1 of the guinea pig hippocampal slice

Dithiothreitol (DTT) is a sulfhydryl reducing agent used as a radioprotectant. Exposure of hippocampal slices for 30 min to 0.5 mM DTT irreversibly increased the orthodromic population spike amplitude, promoted repetitive firing and induced spontaneous epileptiform activity in the CA1 subfield. The same concentration of the oxidized form of DTT did not increase hippocampal excitability. Although the slope of the population synaptic response to afferent stimulation (popPSP) was unchanged by DTT, the duration of the popPSP was prolonged. Recurrent inhibition was unaffected. DTT probably exerts its effects through an irreversible chemical reaction with cellular components. Possible mechanisms of DTT-induced epileptiform activity are discussed.