Increased waking as well as increased synchronization following administration of selective 5-HT uptake inhibitors to...

Sleep and waking stages and EEG power spectra were investigated in rats following saline injections and injection of 10 and 20 mg/kg zimeldine or 10 and 20 mg/kg alaproclate, both selective 5-HT reuptake inhibitors. Following zimeldine there was a biphasic effect on sleep and waking, waking being increased during the first 2 1/2 h of recording, while slow wave sleep (SWS), in particular highly synchronized SWS-2 with high slow wave activity, was increased during the second 2 1/2 h recording period. Analysis of EEG power spectra indicated that the amount of synchronized slow wave activity was also increased within the sleep that occurred during the waking-dominated initial 2 1/2 h period. These data suggest simultaneous appearance of increased waking and increased synchronization following general serotonergic stimulation. They are interpreted as due to effects on different regions of the serotonergic system or on different serotonergic receptors. Consistent with earlier findings, zimeldine also suppressed rapid eye movement (REM) sleep. Following alaproclate, a clear waking effect was present, but only a weak synchronizing effect was seen. This is consistent with data on regional differences in uptake inhibition for zimeldine and alaproclate. Alaproclate also reduced REM sleep. Zimeldine or alaproclate was also administered to rats that had reduced sleep following pretreatment with a moderate dose of parachlorophenylalanine (PCPA). None of the drugs increased waking any further, but the PCPA-pretreated animals that received zimeldine had increased SWS-2, indicating that the SWS-2 increase following zimeldine alone was not a rebound effect.