Effects of glutathione depletion by 2-cyclohexen-1-one on excitatory aminoacids-induced enhancement of activator protein-1 DNA binding in murine hippocampus

We have investigated the role of glutathione in mechanisms associated with excitatory amino acid signaling to the nuclear transcription factor activat or protein-1 (AP1) in the brain using mice depleted of endogenous glutathio ne by prior treatment with 2-cyclohexen-1-one (CHX). In the hippocampus of animals treated with CHX 2 h before, a significant increase was seen in enh ancement of AP1 DNA binding When determined 2 h after the injection of kain ic acid (KA) at low doses. The sensitization to KA was not seen in animals injected with CHX 24 h before, in coincidence with the recovery of glutathi one contents to the normal revels. By contrast, CHX did not significantly a ffect the potentiation by NMDA of API binding under-any experimental condit ions. Prior treatment with CHX resulted in facilitation of behavioral chang es induced by KA without affecting those induced by NMDA. These results sug gest that endogenous glutathione may be at least in part involved in molecu lar mechanisms underlying transcriptional control by KA, but not by NMDA, s ignals of cellular functions.