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

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.

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.

Basic neurophysiology laboratory

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

N/A.

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.

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.