Neonatal treatments with the serotonin uptake inhibitors clomipramine and zimelidine, but not the noradrenaline uptake inhibitor desipramine, disrupt sleep patterns in adult rats.
Chronic postnatal exposure to clomipramine (CMI), a monoamine uptake inhibitor, results in persistent alterations in adult rat REM sleep. These effects have been ascribed to CMI's ability to block neonatal active sleep (AS). However, these effects have not been obtained with other anti-depressants which also block neonatal AS. We compared the long-term effects on adult rat sleep after postnatal treatments (P8-P21) with either CMI or zimelidine (ZMI, a selective serotonin uptake inhibitor) or desipramine (DMI, a selective noradrenaline uptake inhibitor). ZMI and CMI increased the frequency and decreased the duration of REM sleep bouts, increased the number of nonREM-REM transitions, and increased sigma power in REM and nonREM sleep EEGs in adulthood. In contrast, DMI had no effect on any adult sleep parameters. Since ZMI, DMI and CMI all reduce AS to similar levels, these results suggest that neonatal AS suppression is not responsible for the sleep deficits following CMI or ZMI treatment. However, since ZMI and CMI, but not DMI, increase synaptic concentrations of serotonin, elevated serotonin levels during development may instead be responsible for the long-lasting sleep deficits.
Frank
M G
MG
Department of Biological Sciences, Stanford University, CA 94305, USA. mgf@phy.ucsf.edu
Heller
H C
HC
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D002997:Clomipramine / Q000494:pharmacology*; D003891:Desipramine / Q000494:pharmacology*; D004569:Electroencephalography / Q000187:drug effects; D008297:Male; D051381:Rats; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D012890:Sleep / Q000187:drug effects*; D015031:Zimeldine / Q000494:pharmacology*
D018759:Adrenergic Uptake Inhibitors; D002997:Clomipramine; D003891:Desipramine; D017367:Selective Serotonin Reuptake Inhibitors; D015031:Zimeldine