Iranian Journal of Basic Medical Sciences

Iranian Journal of Basic Medical Sciences

Acute and chronic zolpidem administration changes hippocampal long-term potentiation (LTP) as a possible mechanism of memory impairment

Articles in Press

Document Type : Original Article

Authors
Zahra Rezaeiasl 1
Mahmoud Salami 1
Hamid Reza Banafshe 2, 3
1 Physiology Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
2 Department of Pharmacology, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
3 Department of Addiction Studies, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
10.22038/ijbms.2026.95516.20587
Abstract
Objective(s): Zolpidem is a non-benzodiazepine GABAA receptor positive modulator commonly used to treat short-term insomnia. Given its widespread use, understanding its potential impact on cognitive function and synaptic mechanisms is of great interest. This study aimed to investigate the effects of acute and chronic zolpidem administration on hippocampal long-term potentiation (LTP) as a possible mechanism underlying memory impairment in rats.
Materials and Methods: Three groups of rats were used in this study: control, acute (received a single dose of zolpidem, 15 mg/kg), and chronic (received daily doses of zolpidem, 15 mg/kg, for 30 consecutive days). Spatial learning and memory were assessed using the Morris water maze. Basic synaptic transmission and LTP were assessed by recording field excitatory postsynaptic potentials in the hippocampus.
Results: No significant differences were observed in spatial learning among the groups. However, evaluation of spatial memory showed that acute and chronic treatment significantly impaired memory performance compared to the control group. Spatial memory was more severely impaired in the chronic group than in the acute group. Electrophysiological data showed that although LTP was induced in both acute and chronic treatment groups, both had significantly lower LTP magnitude than the control group.
Conclusion: Chronic zolpidem administration caused significantly greater impairment of spatial memory than acute administration, whereas LTP induction was similarly reduced in both groups. These findings suggest that long-term zolpidem use may pose a greater risk to cognitive function than acute exposure.
Keywords
Acute
Chronic
Long-term potentiation
Spatial memory
Zolpidem
Subjects
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Iranian Journal of Basic Medical Sciences

Articles in Press, Accepted Manuscript
Available Online from 22 September 2026