Calcitonin-induced anorexia in rats: Evidence for its inhibitory action on lateral hypothalamic chemosensitive neurons

Abstract

Effects of a synthetic derivative of eel calcitonin, [Asu 1,7]ECT on feeding behavior, and its direct action on the neuronal activity of lateral hypothalamic area (LHA) were studied in rats. Food intake was significantly reduced in a dose-dependent manner after intra-third ventricular injection of [Asu 1,7]ECT (0.2–1.0 U/rat). The neuronal activity of LHA neurons, especially the glucose-sensitive neurons, was inhibited by electrophoretic application of [Asu 1,7]ECT. The inhibition was accompanied by a hyperpolarization of the membrane by about 5–7 mV with an increase in the membrane resistance (5.0–8.7%). This effect was also shown to be independent of noradrenergic or serotonergic mechanisms. Phosphodiesterase inhibitors, such as 3-isobutyl-1-methylxanthine and papaverine augmented the inhibitory response, whereas nicotinic acid blocked it. These results suggest that the anorexia caused by [Asu 1,7]ECT is mediated through a direct inhibition of chemosensitive neuronal activity in the LHA, caused by an increase in the intracellular level of cyclic 3′, 5′-adenosine monophosphate.