We tested whether GABA(A) receptor (R) subunit mRNA levels are homeostatically influenced by short-term exposure to GABA in two adjacent regions of the posterior hypothalamus. mRNA levels for seven GABA(A)R subunits and GABA-synthesizing enzyme (GAD) were quantified in the perifornical (PF) and dorsomedial (DM) hypothalamus following superfusion of slices for 90 min with a drug-free medium, GABA uptake blocker with or without GABA(A)R antagonist, gabazine, or GABA(A)R agonist with tetrodotoxin. Increasing endogenous GABA decreased mRNAs for all seven GABA(A)R subunits in the PF, and for three also in the DM, region; gabazine antagonized these effects in the PF region only and increased GAD-65 mRNA. Stimulation of GABA(A)Rs in the presence of tetrodotoxin decreased mRNA for one GABA(A)R subunit (beta 1). We conclude that, in the PF region where GABA facilitates sleep, increased GABA release may limit GABA(A)R-mediated inhibition, whereas in the DM region, GABA-induced changes are mainly mediated by non-GABA(A) receptors. (c) 2006 Elsevier Inc. All rights reserved.