Antidepressants and REM sleep in Wistar-Kyoto and Sprague-Dawley rats.
Compared to other rat strains, the Wistar-Kyoto rats show increased amount of REM sleep, one of the characteristic sleep changes observed in depressed patients. The aims of this study were firstly to validate a simple sleep stage discriminator and then compare the effect of antidepressants on suppression of rapid eye movement (REM) sleep in Wistar-Kyoto rats and an outbred rat strain (Sprague-Dawley). Rats were implanted with telemetry transmitters with electroencephalogram/electromyogram electrodes. Following recovery, the animals were orally dosed at light onset with either desipramine (20 mg/kg), fluoxetine (10 mg/kg), citalopram (10 or 40 mg/kg) or vehicle in a cross-over design. Every 12-s epoch was automatically scored as WAKE, NREM or REM sleep. Results confirm that Wistar-Kyoto rats show increased amount of REM sleep and decreased REM latency compared with Sprague-Dawley rats. All antidepressants significantly suppressed REM sleep in Sprague-Dawley rats, but only the high dose of citalopram suppressed REM sleep in Wistar-Kyoto rats. These findings suggest that the enhanced REM activity in Wistar-Kyoto rats is less sensitive to the effect of antidepressants and therefore does not provide any additional predictive validity for assessing antidepressant efficacy.
Ivarsson
Magnus
M
Merck Sharp & Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, UK. Magnus_Ivarsson@merck.com
Paterson
Louise M
LM
Hutson
Peter H
PH
D000284:Administration, Oral; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001831:Body Temperature / Q000187:drug effects; D002940:Circadian Rhythm / Q000502:physiology; D015283:Citalopram / Q000494:pharmacology; D018592:Cross-Over Studies; D003891:Desipramine / Q000494:pharmacology; D004569:Electroencephalography; D004576:Electromyography; D005473:Fluoxetine / Q000494:pharmacology; D051381:Rats; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D012895:Sleep, REM / Q000187:drug effects* / Q000502:physiology; D013045:Species Specificity
D000928:Antidepressive Agents; D005473:Fluoxetine; D015283:Citalopram; D003891:Desipramine