Residual Effects of Acute and Subchronic Zolpidem Treatments on Attentional Processes in Aged Female Rats

Zolpidem, a hypnotic Z-drug commonly prescribed to promote sleep, is predominantly used over the age of 50. In this elderly population, adverse behavioral disturbances, impaired driving performance, and an increased risk of falls have been frequently reported. These concerns have raised questions about the residual adverse effects of zolpidem in older adults, particularly on cognitive processes such as executive and attentional functions.

This study aimed to investigate the residual effects of zolpidem on attentional performance following either acute or subchronic administration in aged rats.

A zolpidem dose of 3 mg/kg and a 3-h postadministration time point were selected based on pharmacokinetic data from the literature and a dose-response analysis of its locomotor effects in the open-field test. Attentional performance was then assessed in aged female rats treated with either saline or zolpidem (acutely or for 7 days), using the 5-choice continuous performance task (5C-CPT).

Acute zolpidem administration significantly reduced the percentage of correct responses, increased correct response latency, and showed a trend toward more omissions, indicative of impaired attentional performance and psychomotor slowing. These effects were not further observed after subchronic treatment, suggesting a potential tolerance over time.

Our findings highlight a critical period of vulnerability following the initiation of zolpidem treatment, during which residual cognitive impairments may emerge. Such effects may compromise complex tasks requiring sustained attention and processing speed, such as driving, especially in older adults.