Effects of K-7259 on neuronal activity and synaptic transmission in the rat dorsolateral septal nucleus.

Abstract

K-7259 is a dilazep dihydrochloride derivative that minimizes the damaged area from middle cerebral artery hemiocclusion in the rat (Yamauchi et al. 1992a, b). The effects of K-7259 on the electrophysiological properties of neurons in the rat dorsolateral septal nuclei (DLSN) were examined. K-7259 (100 microM-3 mM) depolarized the membrane with a decrease in input resistance in 36% of the DLSN cells. K-7259 (100 microM) depressed the inhibitory postsynaptic potential (IPSP) and the late hyperpolarizing potential (LHP). The magnitudes of the depressions of the IPSP and LHP with 100 microM K-7259 were 50 +/- 25% (n = 5) and 52 +/- 15% (n = 4), respectively. The amplitudes of the excitatory postsynaptic potentials (EPSPs) were augmented during the inhibition of the IPSP and LHP. However, a voltage-clamp analysis showed that K-7259 did not affect the isolated excitatory postsynaptic current (EPSC). The outward current produced by pressure application of gamma-aminobutyric acid (GABA) to the recording cell was not inhibited by K-7259. These results indicate that K-7259 presynaptically inhibits the IPSP and LHP through a GABAergic pathway.