TY - JOUR T1 - Allopregnanolone Synthesis in Cerebellar Granule Cells: Roles in Regulation of GABA<sub>A</sub> Receptor Expression and Function during Progesterone Treatment and Withdrawal JF - Molecular Pharmacology JO - Mol Pharmacol SP - 1262 LP - 1270 VL - 57 IS - 6 AU - Paolo Follesa AU - Mariangela Serra AU - Elisabetta Cagetti AU - Maria Giuseppina Pisu AU - Stefania Porta AU - Stefania Floris AU - Federico Massa AU - Enrico Sanna AU - Giovanni Biggio Y1 - 2000/06/01 UR - http://molpharm.aspetjournals.org/content/57/6/1262.abstract N2 - Rat cerebellar granule cells were cultured for 5 days with progesterone, resulting in the conversion of progesterone to allopregnanolone, a potent and efficacious modulator of γ-aminobutyric acid (GABA) type-A receptors, as well as in decreases in the abundance of GABAA receptor α1, α3, α5, and γ2 subunit mRNAs. These effects were accompanied by decreases in the efficacies of diazepam and the β-carboline DMCM with regard to modulation of GABA-evoked Cl− currents. Withdrawal from such progesterone treatment resulted in a rapid and selective increase in the abundance of the GABAA α4 subunit mRNA that was associated with a restoration of receptor sensitivity to the negative modulatory action of DMCM, a positive receptor response to flumazenil, and continued reduced responsiveness of receptors to diazepam. Prevention of allopregnanolone synthesis by the 5α-reductase inhibitor finasteride also prevented the changes in both GABAA receptor gene expression and receptor function elicited by progesterone treatment and withdrawal. The American Society for Pharmacology and Experimental Therapeutics ER -