Clomipramine suppresses postnatal REM sleep without increasing wakefulness: implications for the production of depressive behaviors.
Clomipramine (CLI), a REM sleep suppressant, alleviates symptoms of depression in adults but produces depressive behaviors if applied neonatally. Both effects of CLI as applied to adults and to neonates have been interpreted as consequences of its involvement in REM sleep deprivation. However, the paradox of these conflicting effects remains to be understood. The current study attempts to find the possible answer by studying the effects of CLI on postnatal sleep. Eight postnatal rats were evaluated polysomnographically for nine days. Four rats were treated with CLI, 40 mg/kg/day for six days, and four rats were treated with equivolume saline during the same period. The results showed that 1) CLI treatment did not reduce the time of phasic muscle activity which appears during slow wave EEG as it did during REM sleep; 2) during treatment, rats treated with CLI had 44.66%-68.62% REM sleep reduction, varied according to age; 3) REM sleep reduction during treatment was generally compensated by non-REM sleep, so that total sleep (and wakefulness) was comparable to that experienced by rats treated with saline; 4) an obvious REM sleep rebound was observed after drug withdrawal at the age of P19. These results suggest that 1) the stage that shows phasic muscle activity simultaneously with a high amplitude EEG is not REM sleep and is likely to be independent from non-REM sleep in terms of the percentile change; 2) REM sleep reduction without a corresponding increase in wakefulness in postnatal rats is likely the mediator of postnatal RSD in the production of adult depression; and 3) the neuronal bases responsible for REM rebound function by the end of the postnatal third week.
Feng
Pingfu
P
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30306, USA. pfeng@emory.edu
Ma
Yuxian
Y
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D002997:Clomipramine / Q000494:pharmacology*; D003863:Depression / Q000188:drug therapy*; D004195:Disease Models, Animal; D004567:Electrodes, Implanted; D017286:Polysomnography; D051381:Rats; D020318:Rats, Long-Evans; D012895:Sleep, REM / Q000187:drug effects*; D014851:Wakefulness / Q000187:drug effects*
D000929:Antidepressive Agents, Tricyclic; D002997:Clomipramine