The Effects of Imipramine and Fluoxetine on Sleep of Immature Rats

Lee, In Goo; Choi, Byung Jun; Whang, Kyung Tai

Abstract

PURPOSE: Acute administration of non-selective serotonin (5-HT) reuptake inhibitor such as imipramine and selective 5-HT reuptake inhibitor, like fluoxetine leads, to an increase of extracellular 5-HT concentration in the brain. We sought to determine the average time spent asleep, the frequency of REM sleep, and the percent of REM and NREM sleep in the total sleep time in saline (sham-treated control) (n=6), imipramine (n=8), or fluoxetine (n=6)-treated animals.
METHODS
Right and left cortical and hippocampal electrodes were placed in 10-15 day old Sprague-Dawley rats. The following day 2 hour video EEG recordings were done to monitor sleep induced by intraperitoneal injection of saline, imipramine (10mg/kg), or fluoxetine (10mg/kg) after getting a baseline EEG during 30 minutes. And data were analyzed using t-test.
RESULTS
1) Following intraperitoneal injection of saline, imipramine, or fluoxetine, there were no epileptiform features or changes in the EEG except for a difference in sleep cycling. 2) The percent of average time spent asleep was significantly greater for control (87.8%) and fluoxetine-treated animals (92%) compared to imipramine-treated animals (66.1 %) (p<0.005). 3) The average frequency of REM sleep was 11.2 in control, 0.1 in imipramine-treated animals, and 8.7 in fluoxetine-treated animals, respectively during the 2 hours. And the frequency of REM sleep was significantly less for imipramine-treated animals compared to control (p<0.002). 4) Control animals (41.2%) spent significantly less time in NREM sleep compared to imipramine (98.8%)- and fluoxetine (93%)-treated animals (p<0.0001) and significantly more time (58.8%) in REM sleep compared to both imipramine (1.2%)- and fluoxetine (7%) treated animals (p<0.0001).
CONCLUSION
We confirmed that postnatal 10-15 day old rats spent more time in REM sleep than NREM sleep, and acute administration of imipramine or fluoxetine increased NREM sleep by decreasing the frequency and the duration of REM sleep by 5-HT reuptake inhibition in the brain.