The GABA A receptor agonist THIP is neuroprotective in organotypic hippocampal slice cultures

Abstract

The potential neuroprotective effects of the GABA A receptor agonists THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol) and muscimol, and the selective GluR5 kainate receptor agonist ATPA (( RS)-2-amino-3-(3-hydroxy-5- tert-butylisoxazol-4-yl)propanoic acid), which activates GABAergic interneurons, were examined in hippocampal slice cultures exposed to N-methyl- d-aspartate (NMDA). The NMDA-induced excitotoxicity was quantified by densitometric measurements of propidium iodide (PI) uptake. THIP (100–1000 μM) was neuroprotective in slice cultures co-exposed to NMDA (10 μM) for 48 h, while muscimol (100–1000 μM) and ATPA (1–3 μM) were without effect. The results demonstrate that direct GABA A agonism can mediate neuroprotection in the hippocampus in vitro as previously suggested in vivo.