Intranasal Dexamethasone Selectively Impairs Exploratory and Learning Behaviour While Sparing Peripheral Metabolic...

Area of Science:

• Neuroscience
• Pharmacology
• Endocrinology

Background:

• Dexamethasone (Dex) is a synthetic glucocorticoid used clinically.
• Systemic administration causes metabolic and cognitive side effects.
• Intranasal Dex offers targeted brain delivery, but its effects require clarification.

Purpose of the Study:

• To investigate the effects of repeated intranasal Dex administration on metabolic, behavioral, and neurochemical endpoints in mice.
• To assess the safety and efficacy of intranasal Dex for brain delivery.

Main Methods:

• Adult male mice received daily intranasal Dex (5, 15, 50 μg/kg) or saline for seven days.
• Evaluated body weight, glucose metabolism, insulin levels, and corticosterone.
• Assessed behavior using Morris Water Maze, Elevated Plus Maze, Open Field Test, and Novel Object Recognition Test.
• Analyzed brain tissue for oxidative stress, acetylcholinesterase activity, and trace minerals.

Main Results:

• Intranasal Dex did not alter body weight, glucose control, insulin sensitivity, or corticosterone levels.
• Observed dose-dependent decreases in locomotor activity and spontaneous alternation.
• Increased escape latencies in spatial learning tests, but no effect on memory retention or object recognition.
• Brain oxidative stress and major minerals remained stable; acetylcholinesterase activity showed a downward trend.

Conclusions:

• Seven-day intranasal Dex selectively impairs exploratory behavior and learning acquisition in mice.
• Effects are mediated by central glucocorticoid receptors, impacting synaptic and cholinergic function.
• Intranasal Dex preserves peripheral metabolic and oxidative balance, indicating targeted central effects.