Changes in GABAA Receptor Gene Expression Induced by Withdrawal of, but Not by Long-Term Exposure to,

The effects of ganaxolone, a synthetic analog of the endogenous neuroactive steroid allopregnanolone, on the function and expres-sion of GABAA receptors were determined. Electrophysiological recordings demonstrated that ganaxolone potentiated with a po-tency and efficacy similar to those of allopregnanolone the Cl currents evoked by GABA at recombinant human GABAA recep-tors (comprising 122L or 222L subunit assemblies) ex-pressed in Xenopus oocytes. Exposure of cultured rat cerebellar granule cells to 1 M ganaxolone for 5 days had no effect on the abundance of mRNAs encoding the 1, 2, 3, 4, 5, 2L, or 2S subunits of the GABAA receptor. Withdrawal of ganaxolone after such long-term treatment, however, induced an increase in the abundance of 2, 4, and 5 subunit mRNAs and a decrease in the amounts of 1, 2L, and 2S subunit mRNAs. Thes