Effects of Melatonin Administration in Different Time Modes on Morphofunctional Indices of the Hypothalamic Serotonergic Neurons in Obese Rats

We examined the effects of introduction of melatonin in different time modes on morphofunctional parameters of serotonergic neurocytes of the rat hypothalamic arcuate nucleus (cross-sectional area of the neurocyte nuclei, content of serotonin vesicles per neuron, and number/density of serotonergic neurons); general levels of tryptophan and serotonin in the rat brain were also estimated. Experimental animal groups included rats with normal body mass and rats with obesity induced by a high-calorie diet; three different modes of melatonin introduction were used (single introductions by gavage in the morning, similar introductions in the evening, and continuous introduction with drinking water, i.e., distributed in time). Animals with high-calorie diet-induced obesity were characterized by a greater mean area of cross-sections of the neurocyte nuclei, a smaller number of serotonin-positive neurocytes, and smaller numbers of serotonin-containing vesicles in each neurocyte of the arcuate nucleus. The levels of serotonin and its precursor tryptophan in the brain were also smaller in the above (obese) rats. Introductions of melatonin into rats fed a high-calorie diet provided relative smoothing of the abovementioned changes: the dimensions of the neurocyte nuclei became close to the control values. The number of serotonin-positive neurons increased (only at evening and time-distributed introductions), the number of serotonin-containing vesicles was greater (exclusively at distributed melatonin introductions), and the general contents of serotonin and tryptophan in the brain also increased (at evening and distributed introductions). The mode of continuous distributed introduction of melatonin with drinking water was found to be most effective. Thus, introductions of melatonin improve the functional state of serotonergic neurocytes in the hypothalamic arcuate nucleus of rats with moderate pathological manifestations of obesity; the intensity of melatonin-induced morphofunctional shifts depends noticeably on the time mode of its introduction.