ASTROGLIA-RELEASED FACTOR SHOWS SIMILAR EFFECTS AS BENZODIAZEPINE INVERSE AGONISTS

Media conditioned by cultured neonatal cerebral cortex microexplants ( CCM) or astrocytes (ACM) contain low molecular weight (<1,000 Da) subs tance(s) which inhibits the gamma aminobutyric acid (GABA)-induced inw ard current recorded in cerebellar granule cells and hippocampal neuro ns in culture using the whole-cell patch-clamp technique. This effect is specific for CCM and ACM, as medium conditioned by PC12 cells (PC12 CM) does not affect the GABA response of these cells. It is also speci fic for GABA-induced currents because glutamate-induced currents do no t change either in amplitude or in shape in the presence of CCM or ACM . The inhibitory effect on the GABA response in cerebellar granule cel ls of both ACM and CCM could be suppressed by flumazenil, a specific b enzodiazepine (BZD) antagonist and could be mimicked by two BZD invers e agonists. These data thus demonstrate the presence of a BZD inverse agonist-like activity in CCM and ACM. This effect of ACM on different neuronal cell types was heterogenous since no detectable effect could be observed on the GABA-induced current in GABA-responsive dorsal root ganglion (DRG) neurons, presumably reflecting a functional heterogene ity of the GABAA receptors present in these different neuronal subsets . By the release of such an endogenous BZD inverse agonist-like activi ty, glia cells could possibly modulate CABA(A), receptor-mediated resp onses. (C) 1994 Wiley-Liss, Inc.