Acute activation of estrogen receptors (ERs) increases release probability from POMC neurons through a rapid, non-genomic mechanism. A, Within 10 min of E2 (100 nM) addition to the bath, the PPR is decreased, that is release probability is increased. The rapidity of this effect suggests a non-genomic mechanism of action. B, Bath application of STX (10 nM), an agonist selective for a Gq-coupled membrane ER, was similarly able to decrease the PPR in cells from intact males and OVX females. C, The decrease in PPR following addition of STX to the bath was statistically significant in OVX females (paired t test, ** p < 0.01). D, Pre-treatment with cycloheximide did not prevent the effects of STX, indicating changes in transcription/translation were not necessary. Traces are the average of 50 sweeps.