17β-estradiol (E2) is a sex hormone that regulates gene expression in the reproductive system. In addition to these genomic effects that take place over a relatively long time scale, a growing body of evidence points to rapid effects of E2 mediated by a plasma membrane receptor. In the present study, we examined the acute effects of E2 on the electrical excitability of neurons from the Locus Coerulus. Brain slices containing the Locus Coerulus were obtained from neonatal Wistar rats of post-natal day p5-7, and membrane potentials were recorded using standard intracellular techniques with sharp glass microelectrodes. Resting membrane potentials were -65±6 mV (N=27). Locus Coerulus neurons presented spontaneous action potentials or subthreshold oscillations. Spontaneous action potentials (N=3) or sub-threshold oscillations (N=8) were reversibly abolished within minutes of application of E2 encapsulated in hydroxypropyl-β-cyclodextrin (HBCD; 200 nM). In addition, application of E2 caused a membrane hyperpolarization of 4.9±2.5 mV (N=8). Effects of E2 were completely reversible upon washout, and could be repeated multiple times in the same cell (up to 8 applications over 6 hours) with similar results. Application of the encapsulation vehicle HBCD alone caused no effect (N=4). To determine if the receptor activated by E2 was on the cell surface or intracellular, we tested E2 conjugated to Bovine Serum Albumin (E2-BSA) on LC activity. Similar to encapsulated E2, E2-BSA inhibited spontaneous activity and hyperpolarized the membrane (N=4). We conclude that E2 can inhibit the spontaneous activity of Locus Coerulus neurons by interaction with a plasma membrane receptor.