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Many studies are currently addressing the involvement of orexin-containing hypothalamic neurons in the responses of the CNS to administration of antigens, particularly lipopolysaccharide (LPS). The dynamics of changes in the number of orexin-containing neurons in hypothalamic structures in brain slices were assessed 2, 4, and 6 h after administration of LPS at a low, non-septic dose. Comparative analysis of the responses of orexin-containing neurons after administration of a non-septic and a higher, subseptic, dose of LPS was performed. LPS at a dose of 25 μg/kg was followed 2 and 4 h later by increases in the numbers of orexin-positive neurons, with subsequent decreases in numbers, while the higher LPS dose of 500 μg/kg altered the neuron count only at 6 h, with a more significant decline in the number of orexin-containing neurons. These data provide evidence for changes in the content of orexin detected within neurons and a change in the balance of orexin synthesis and utilization processes in response to administration of an antigen.