Chronic treatment with ionotropic glutamate receptor antagonist kynurenate affects GABAergic synaptic transmission in rat hippocampal cell cultures

It is well documented that prolonged treatment with antagonists of ionotropic glutamate receptors activates a number of homeostatic mechanisms including alteration of glutamatergic transmission. We studied whether this treatment can also affect GABAergic transmission. Using whole-cell voltage clamp recording and local extracellular stimulation we investigated evoked inhibitory postsynaptic currents (IPSCs) in cultured rat hippocampal neurons grown in the presence of ionotropic glutamate receptor antagonist kynurenate (I mM) and in control conditions. Chronic kynurenate treatment did not significantly affect the amplitude of evoked IPSCs and IPSC reversal potentials. In contrast we found that the paired-pulse depression was increased by 67% in cultures treated with kynurenic acid. We conclude that additional mechanism(s), alteration of GABAergic synaptic transmission, may contribute to homeostatic plasticity induced by chronic block of ionotropic glutamate receptors. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.