The non-benzodiazepine hypnotic zolpidem impairs sleep-dependent cortical plasticity.
OBJECTIVE
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.


METHODS
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.


METHODS
Basic neurophysiology laboratory


METHODS
Cats (male and female) in the critical period of visual development (postnatal days 28-41)


METHODS
N/A.


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.
Department of Neuroscience, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Julie
J
Seibt
Sara J
SJ
Aton
Sushil K
SK
Jha
Tammi
T
Coleman
Michelle C
MC
Dumoulin
Marcos G
MG
Frank
D000818:Animals; D001931:Brain Mapping; D002415:Cats; D002540:Cerebral Cortex / Q000187:drug effects*; D004292:Dominance, Cerebral / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000187:drug effects; D005074:Evoked Potentials, Visual / Q000187:drug effects; D005260:Female; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D007192:Indenes / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects*; D017286:Polysomnography / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology*; D012815:Signal Processing, Computer-Assisted; D012890:Sleep / Q000187:drug effects*; D012894:Sleep Stages / Q000187:drug effects; D041623:Tomography, Optical Coherence; D014229:Triazolam / Q000494:pharmacology; D000077334:Zolpidem
D006993:Hypnotics and Sedatives; D007192:Indenes; D011725:Pyridines; D014229:Triazolam; D000077334:Zolpidem; C495910:ramelteon