Leptin affects the electrical activity of neurones in the hypothalamic supraoptic nucleus

The present experiments were undertaken to examine whether leptin affects the electrical activity of neurones in the supraoptic nucleus (SON) by using brain slice preparation of male Wistar and obese Zucker rats. Bath application of leptin (10(-8) - 10(-12) M) induced mainly inhibitory response in SON neurones of Wistar rats, although a minority showed excitation. These effects were observed in both continuously and phasically active cells. The inhibitory effect of leptin still persisted in low Ca(2+), high Mg(2+) medium. Bath application of tolbutamide, which is known to inhibit ATP-sensitive potassium channel activity, did not reverse the inhibitory effect of leptin on SON neurones. The effect of bath application of leptin was also tested in SON neurones of obese Zucker rats. Although leptin still affected the electrical activity of some SON neurones of Zucker rats, the proportion of unaffected neurones was significantly higher than in Wistar rats. The results suggest that leptin may inhibit the secretion of both oxytocin and vasopressin by inhibiting the electrical activity of neurones in the SON via direct action. This inhibitory effect of leptin may be exerted through mechanisms other than activation of ATP-sensitive potassium channels.