Fig. 5.

E₂ and the Gq-mER ligand STX differentially modulate the GABA_B response in NPY/AgRP cells from gonadectomized mice. A–F: representative traces of GABA_B responses from ovariectomized (OVX) females before and after application of E₂ or STX with or without additional pharmacological manipulations (see below). Experiments were conducted as shown in Fig. 1. Dotted line represents baseline current. V_hold = −50 mV. Vertical scale bars represent 20 pA; horizontal ones represent 5 min. For illustrative purposes, most of the 15-min treatment period between GABA_B responses (R1 and R2) is removed. Other small breaks in the recording indicate removal of slightly prolonged return to baseline current levels following baclofen application. G: bar graphs summarizing effects of E₂ and STX (both 100 nM) on the GABA_B response (baclofen, 10 μM) in NPY/AgRP neurons. In OVX females, baclofen elicited 2 equal-amplitude responses during perfusion of vehicle (n = 4), but E₂ suppressed (n = 7), enhanced (n = 11), or had no net effect (n = 6) on the GABA_B response. Coperfusing a PI3K inhibitor (WRT, 100 nM, n = 6) with E₂ or simply applying STX (n = 5) purely enhanced the response. E₂ similarly affected the GABA_B response in orchidectomized (ORCH) males (see results) and coperfusing wortmannin (n = 4) isolated the enhancement. *P < 0.05, **P < 0.01, vs. vehicle control group.