The methanolic extract of Withania somnifera acts on GABA_A receptors in gonadotropin releasing hormone (GnRH) neurons in mice

The effect of the methanol extract of Withania somnifera (mWS) on the gonadotropin releasing hormone (GnRH) neuron was examined in juvenile mice using the whole cell patch clamp technique. GnRH neurons are the fundamental regulators of the pulsatile release of GnRH needed for puberty and fertility. GnRH neurons were depolarized by bath application of the mWS (400 ng/μl) under the condition of a high Cl^- pipette solution in current clamp mode. In voltage clamp mode, mWS induced reproducible inward currents (31.7 ± 5.51 pA, n = 14). The mWS-induced inward currents persisted in the presence of tetrodotoxin (TTX, 0.5 μM), but were suppressed by bicuculline methiodide (BMI, 20 μM), a GABA_A receptor antagonist. These results show that mWS affects the neuronal activities by mediating the GABA _A receptor, which suggests that WS contains an ingredient with possible GABAmimetic activity.