RT Journal Article SR Electronic T1 Allopregnanolone Synthesis in Cerebellar Granule Cells: Roles in Regulation of GABAA Receptor Expression and Function during Progesterone Treatment and Withdrawal JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 1262 OP 1270 VO 57 IS 6 A1 Paolo Follesa A1 Mariangela Serra A1 Elisabetta Cagetti A1 Maria Giuseppina Pisu A1 Stefania Porta A1 Stefania Floris A1 Federico Massa A1 Enrico Sanna A1 Giovanni Biggio YR 2000 UL http://molpharm.aspetjournals.org/content/57/6/1262.abstract AB 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