Effects of the androgenic/anabolic steroid stanozolol on GABAA receptor function: GABA-stimulated 36Cl- influx and [35S] TBPS binding.

We have recently demonstrated that androgenic/anabolic steroids modulate in vitro ligand binding to the benzodiazepine binding site(s) associated with the gamma-aminobutyric acidA (GABAA) receptor complex (Masonis and McCarthy, 1995). One androgenic/anabolic steroid in particular, stanozolol, appears to stabilize the GABAA receptor in a moderate-affinity state for benzodiazepine binding. In the present study, we demonstrate the effects of stanozolol on the functional responsiveness of the GABAA receptor. After pre-incubation with stanozolol, we observed a decrease in the Emax and EC50 values for GABA-stimulated 36Cl- influx into cortical synaptoneurosomes. Moreover, in the presence of stanozolol, flunitrazepam-enhanced GABA-stimulated 36Cl- influx was lost, and the GABAA receptor was stabilized in a functional state that was resistant to further desensitization by agonist. Stanozolol does not appear to reduce GABA-stimulated 36Cl- influx by acting as a channel blocker at the well-characterized channel blocker binding site, as illustrated by the GABA-sensitive biphasic effects of stanozolol on [35S] t-butylbicyclophosphorothionate binding. These results demonstrate a novel, nongenomic mechanism for androgenic/anabolic steroidal modulation of CNS function.