Effects of mazindol on rat lateral hypothalamic neurons

In order to elucidate the mechanism of action of the anorectic drug, mazindol, effects of electrophoretically applied mazindol were examined on glucose-sensitive and non glucose-sensitive neurons in the rat lateral hypothalamic area (LHA), which is functionally important in food intake control. Mazindol was found to significantly suppress the firing rate of glucose-sensitive neurons. Ouabain a Na-K pump inhibitor, attenuated mazindol induced suppression of neuronal firing rate. Intracellular recordings revealed hyperpolarization of the membrane with no change in membrane conductance by perfusion of brain slice with 0.1 mM mazindol in bath. This was similar to the effect of 30 mM glucose. Results suggest that the inhibitory action of mazindol is mediated by activation of the Na-K pump. Spiroperidol, a dopamine antagonist, did not affect the inhibitory response to mazindol, suggesting direct action of mazindol on LHA neurons, independent of dopamine.