Does ACTH4-9 prevent behavioral impairment induced by dexamethasone (DEX) at higher doses?
Keywords:
glucocorticoids, dexamethasone, ACTH4-9, behavioral tests, neurodegeneration, neuroprotection, miceAbstract
Glucocorticoids (GCs) are used therapeutically for their potent anti-inflammatory and immunosuppresive properties in the treatment of allergic, rheumatologic, neurological and autoimmune diseases. GCs and their preparations, such as dexamethasone (DEX), which are often administered chronically in high doses, can induce neuronal damage of the brain, especially hippocampus (with high concentration of GCs receptors) that plays an important role in memory, mood and behavior. Our studies, as well as the studies conducted by other authors, reveal neuroprotective effect of ACTH4-9 -(-synthetic adrenocorticotropin-4-9-analog) in some models of central and peripheral neuronal degeneration. The aim of this study was to investigate the influence of ACTH4-9 (at the dose of 50 and 100 mg/kg/twice a week) on impairment of behavioral effects of mice subjected to neurotoxic activity of DEX (at the doses of 40 and 80 mg/kg/day). The results of the study showed that DEX, at either dose, impaired the motor coordination (“chimney” test), decreased memory acquisition in the step-through passive avoidance test, evoked significant lethality and decreased the body weight of mice. During 28 days of experiment, ACTH4-9, at specified doses, had no impact on the behavioral effects or on the lethality of mice, but on the increase of body weight. ACTH4-9, at the dose of 100 mg/kg (but not 50 mg/kg), improved the behavioral effects but did not diminish the lethality or body weight of mice treated with DEX at either dose. The above findings confirm the neuroprotective properties of ACTH4-9 in mice exposed to neurotixic activity of DEX.
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