Which statement describes allopregnanolone's action on GABA receptors?

• A. It directly activates GABAA receptors
• B. It inhibits GABA synthesis
• C. It is a negative allosteric modulator of GABAA receptors
• D. It is a positive allosteric modulator of the GABAA receptor

Answer: (D)

Allopregnanolone enhances the brain’s inhibitory signaling by binding to a neurosteroid site on the GABAA receptor and increasing how well the receptor responds to GABA. This is positive allosteric modulation: it doesn’t activate the receptor by itself at normal concentrations, but it makes GABA more effective at opening the chloride channel, strengthening inhibitory currents. This increased chloride influx hyperpolarizes neurons and dampens excitability. It’s not about reducing GABA synthesis, nor about blocking the receptor, and while very high concentrations can directly gate the channel, the physiologic action described here is boosting GABA’s effect, i.e., a positive allosteric modulator.