Korean J Physiol Pharmacol.  2012 Aug;16(4):231-236. 10.4196/kjpp.2012.16.4.231.

Effects of Single Treatment of Anti-Dementia Drugs on Sleep-Wake Patterns in Rats

• Jung JY
• Roh M
• Ko KK
• Jang HS
• Lee SR
• Ha JH
• Jang IS
• Lee HW
• Lee MG

• KMID: 2011156
• DOI: http://doi.org/10.4196/kjpp.2012.16.4.231

Abstract

We studied the effects of acetylcholinesterase inhibitors, donepezil and galantamine, and an N-methyl-D-aspartate (NMDA) receptor blocker, memantine, on sleep-wake architecture in rats. Screw electrodes were chronically implanted into the frontal and parietal cortex for the electroencephalography (EEG). EEG was recorded with a bio-potential amplifier for 8 h from 09:30 to 17:30. Vibration was recorded to monitor animal activity with a vibration measuring device. Sleep-wake states such as wake (W), slow-wave sleep (S) and paradoxical or rapid eye movement sleep (P), were scored every 10 sec by an experimenter. We measured mean episode duration and number of episode to determine which factor sleep disturbance was attributed to. Donepezil and memantine showed a significant increase in total W duration and decreases in total S and P duration and delta activity. Memantine showed increases in sleep latency and motor activity. Changes of S and P duration in memantine were attributed from changes of mean episode duration. Galantamine had little effect on sleep architecture. From these results, it is showed that galantamine may be an anti-dementia drug that does not cause sleep disturbances and memantine may be a drug that causes severe sleep disturbance.

Keyword

Donepezil; Electroencephalography; Galantamine; Memantine; Sleep-wake state

MeSH Terms

Animals
Cholinesterase Inhibitors
Electrodes
Electroencephalography
Galantamine
Indans
Memantine
Motor Activity
N-Methylaspartate
Organothiophosphorus Compounds
Piperidines
Rats
Sleep, REM
Vibration
Cholinesterase Inhibitors
Galantamine
Indans
Memantine
N-Methylaspartate
Organothiophosphorus Compounds
Piperidines

Figure

• 

  Fig. 1 (A) Total duration (min), (B) number of episode (per 2-h period) and (C) mean episode duration of each sleep-wake stages after drug treatment. The rats were given saline (Con), galantamine (Gal), donepezil (Don) and memantine (Mem). Two-h period following each drug treatment was scored. Data were expressed as mean±S.E.M. (n=8 per group). *p<0.05 and **p<0.01; significantly different from the Con group. W, active and quiet wake; S, transition to slow-wave sleep and slow-wave sleep; and P, transition to paradoxical sleep and paradoxical sleep.

• 

  Fig. 2 (A) Latency to 5-min S and to 1-min P. (B) Delta activity in the frontal and parietal cortex for 2-h period after drug treatment. (C) Vibration. The rats were given saline (Con), galantamine (Gal), donepezil (Don) and memantine (Mem). Data were expressed as mean±S.E.M. (n=8 per group). *p<0.05, **p <0.01 and ***p<0.001: significantly different from the Con group. S, transition to slow-wave sleep and slow-wave sleep, and P, transition to paradoxical sleep and paradoxical sleep.

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