Modulation of recombinant GABA(A) receptors by neurosteroid dehydroepiandrosterone sulfate.

Aim: To investigate whether long-term exposure to the neurosteroid dehydroepiandrosterone sulfate (DHEAS) induces adaptive changes of GABA(A) receptors related to the development of tolerance and dependence.

Methods: We compared the parameters of [(3)H]DHEAS binding and the effects of DHEAS on [(3)H]flunitrazepam binding in the membranes of HEK 293 cells, nontransfected or stably transfected with recombinant α(1)β(2)γ(2S) GABA(A) receptors. In HEK 293 cells expressing α(1)β(2)γ(2S) GABA(A) receptors, we investigated the effects of long-term DHEAS treatment on the [(3)H]flunitrazepam and [(3)H]t-butylbicycloorthobenzoate ([(3)H]TBOB) binding and on their modulation with GABA.