The Non-Benzodiazepine Hypnotic Zolpidem Impairs Sleep-Dependent Cortical Plasticity
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STUDY OBJECTIVES: The effects of hypnotics on sleep-dependent brain plasticity are unknown. We have shown that sleep enhances a canonical model of in vivo cortical plasticity, known as ocular dominance plasticity (ODP). We investigated the effects of 3 different classes of hypnotics on ODP. DESIGN: Polysomnographic recordings were performed during the entire experiment (20 h). After a baseline sleep/wake recording (6 h), cats received 6 h of monocular deprivation (MD) followed by an i.p. injection of triazolam (1-10 mg/kg i.p.), zolpidem (10 mg/kg i.p.), ramelteon (0.1-1 mg/kg i.p.), or vehicle (DMSO i.p.). They were then allowed to sleep ad lib for 8 h, after which they were prepared for optical imaging of intrinsic cortical signals and single-unit electrophysiology. SETTING: Basic neurophysiology laboratory PATIENTS OR PARTICIPANTS: Cats (male and female) in the critical period of visual development (postnatal days 28-41) INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Zolpidem reduced cortical plasticity by approximately 50% as assessed with optical imaging of intrinsic cortical signals. This was not due to abnormal sleep architecture because triazolam, which perturbed sleep architecture and sleep EEGs more profoundly than zolpidem, had no effect on plasticity. Ramelteon minimally altered sleep and had no effect on ODP. CONCLUSIONS: Our findings demonstrate that alterations in sleep architecture do not necessarily lead to impairments in sleep function. Conversely, hypnotics that produce more "physiological" sleep based on polysomnography may impair critical brain processes, depending on their pharmacology.
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Muscimol and zolpidem impair sleep-dependent plastic changes in visual cortex in cats, suggesting GABA plays critical role for plastic processes during sleep.
“Conversely, the GABA A agonist muscimol and also zolpidem impaired sleep-dependent plastic changes in the visual cortex in a developmental model of synaptic plasticity in cats [i.e., ocular dominance plasticity (ODP); see sect.VIIA3 for details] (48,411,1059), suggesting that GABA plays a critical role for plastic processes occurring during sleep.”
From About Sleep's Role in Memory (2013) · cites this paper as [1059]
Of zaleplon, eszopiclone, zolpidem, and triazolam, only zolpidem impaired sleep-dependent ODP, although all reduced REM sleep and increased non-REM sleep.
“Of the GABA A agonistic substances zaleplon, eszopiclone, zolpidem, and triazolam, only zolpidem impaired sleep-dependent ODP, although all substances distinctly reduced REM sleep and increased non-REM sleep (48,1059).”
From About Sleep's Role in Memory (2013) · cites this paper as [1059]
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- Authors
- Seibt, J., Aton, S. J., Jha, S. K., Coleman, T., Dumoulin, M., & Frank, M. G.
- Affiliations
- University of Pennsylvania (US)
- Jawaharlal Nehru University (IN)
- Corresponding author
- Marcos Gabriel Frank
- Venue
- Sleep
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-10-01
- Volume
- 31
- Issue
- 10
- Pages
- 1381-91
- ISSN
- 0161-8105 (ISSN-L)
- 1550-9109
- PMC
- PMC2572743
- OpenAlex
- W2150658436
- Cited by
- 60
- References
- 61
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 3 · 2022: 7 · 2021: 4 · 2020: 2 · 2019: 2 · 2018: 6 · 2017: 4 · 2015: 3 · 2014: 3 · 2013: 6 · 2012: 4
- FWCI
- 2.42
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- SLEEP (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Eye Institute (F32EY017766, T32EY007143)
- National Institute of General Medical Sciences (T32GM07517, T32GM007517)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- zolpidem, hypnotics, ocular dominance plasticity, cortical plasticity, monocular deprivation, triazolam, ramelteon, sleep architecture, visual development, critical period, cats
- MeSH terms
- Zolpidem, Animals, Brain Mapping, Cats, Cerebral Cortex, Dominance, Cerebral, Dose-Response Relationship, Drug, Electroencephalography, Evoked Potentials, Visual, Female, Hypnotics and Sedatives, Indenes, Injections, Intraperitoneal, Male, Neuronal Plasticity, Pyridines, Signal Processing, Computer-Assisted, Sleep, Sleep Stages, Triazolam, Polysomnography, Tomography, Optical Coherence
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