Effects of Dexmedetomidine on the Behavioral Outcomes in Streptozotocin‐Induced Alzheimer's Disease Rats

TL;DR

Dexmedetomidine at 25 µg/kg improves memory in rats with Alzheimer's disease induced by streptozotocin, suggesting it could be a potential treatment.

Contribution

The study identifies a specific dose of dexmedetomidine that reverses cognitive deficits in an Alzheimer's rat model.

Findings

Dexmedetomidine at 25 µg/kg reversed STZ-induced memory impairment in Y-maze and Morris Water Maze tests.

Higher doses of dexmedetomidine did not provide additional cognitive benefits.

Dexmedetomidine's effects are likely due to neuroprotective and anti-inflammatory mechanisms.

Abstract

Alzheimer's disease (AD) is a progressive and prevalent neurodegenerative disorder characterized by progressive cognitive decline and memory impairment. Intracerebroventricular (ICV) administration of streptozotocin (STZ) in rodents recapitulates key features of sporadic AD, including brain insulin resistance and oxidative stress. Dexmedetomidine (Dex), a highly selective α2‐adrenergic receptor agonist, has demonstrated neuroprotective and anti‐inflammatory properties, suggesting its potential utility as a therapeutic approach for AD.

Seventy adult male Wistar rats were randomly allocated to seven experimental groups: Control, Sham, STZ, Sham + Dex (25 µg/kg), and STZ + Dex (25, 50, 100 µg/kg). Cognitive performance and anxiety‐like behaviors were evaluated using the open‐field test (OFT), elevated plus maze (EPM), Y‐maze test, and Morris water maze (MWM).

In the Y‐maze, STZ‐treated rats exhibited significant reductions in spontaneous alternation behavior (p = 0.002), which were significantly reversed by Dex (25 µg/kg, p = 0.002). In the MWM, the STZ administration resulted in prolonged escape latencies and increased path lengths compared with Control animals (p < 0.05). Treatment with Dex (25 µg/kg) significantly improved spatial learning and memory retention (p < 0.05). No significant differences were observed in locomotor activity and anxiety‐related behaviors in the OFT or EPM.

These findings indicate that Dex at 25 µg/kg attenuates STZ‐induced cognitive deficits, likely through neuroprotective and anti‐inflammatory mechanisms. The results highlight Dex as a promising candidate for AD therapy, though further research is required to elucidate its underlying molecular pathways. The study supports the potential repurposing of Dex for neurodegenerative disorders.

Dexmedetomidine at 25 µg/kg effectively reverses working and spatial memory deficits in a streptozotocin (STZ)‐induced rat model of Alzheimer's disease, restoring Y‐maze alternation and Morris Water Maze performance. Higher doses show no clear benefit, highlighting Dex‐25 as a promising neuroprotective candidate.

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