Effect of noradrenergic denervation of medial prefrontal cortex and dentate gyrus on recovery after sleep deprivation in the rat.

The noradrenergic-locus coeruleus (LC) system has a regulatory influence on forebrain neuronal networks. We have previously shown that the amygdala is strongly implicated in the mechanism of rebound seen after a 10 h sleep deprivation (SD). In the present study, our objective was to determine whether the medial prefrontal cortex and dentate gyrus (DG) which receive an important innervation from the LC, play a role in the rebound mechanisms. We found that microinjection of the specific noradrenergic neurotoxin, N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine, into these regions had no effect on the increase in paradoxical sleep duration seen after SD, suggesting that noradrenergic (NA) innervation of the prefrontal cortex and DG are not involved in sleep rebound regulation.

Effect of noradrenergic denervation of the amygdala upon recovery after sleep deprivation in the rat.

We previously showed that the noradrenergic locus coeruleus (NA-LC) was involved in the regulatory mechanisms of the paradoxical sleep rebound following a 10 h sleep deprivation by using a systemic injection of a specific neurotoxin, N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4). Given that rebound mechanisms are mainly located in the forebrain, we planned to study the role of the forebrain structures receiving LC afferences. In this study we evaluated the involvement of noradrenergic afferences to the central nucleus of the amygdala in the sleep rebound by DSP-4 microinjections into the central nucleus of the rat amygdala. The results showed that during the first recovery day, the paradoxical sleep rebound is lower in DSP-4 treated rats (-67.28%). These findings indicate that the amygdala, through its NA afferents, contributes to the sleep rebound mechanisms.

Renin as a biological marker of the NREM-REM sleep cycle: effect of REM sleep suppression.

We have previously described that, in normal man, the nocturnal oscillations of plasma renin activity (PRA) exactly reflect the rapid eye movement (REM)-non(N)REM sleep cycles, with increasing PRA levels during NREM sleep and decreasing levels during REM sleep. This study was carried out to determine whether REM sleep suppression affects nocturnal renin profiles and to define which sleep stage is essential for renin release. In a first experimental series, REM sleep was suppressed by using clomipramine, a tricyclic antidepressant. Seven healthy young men were studied once during a night when a placebo was given and once during a night following a single dose of 50 mg clomipramine. Blood was collected every 10 min from 23.00 hours to 07.00 hours. PRA was measured by radio-immunoassay and the nocturnal profiles were analysed using the pulse detection program ULTRA. Clomipramine suppressed REM sleep in all subjects but one, but did not affect the number of SWS episodes nor their duration. Similar PRA profiles were observed in both experimental conditions. Neither the mean levels, nor the number and the amplitude of the oscillations were modified and the normal relationship between slow wave sleep and increasing PRA levels was preserved. In a second experimental series, REM sleep was prevented by rapidly awakening the subjects as soon as they fell into REM sleep. The four subjects studied attempted several times to go into REM sleep, but only when PRA levels were decreasing. The interruption of REM sleep by short waking periods did not disturb PRA for which the oscillations remained unaffected. Again, the relationship between SWS and increasing PRA levels was preserved. These results provide evidence that mechanisms increasing slow-wave activity are principally involved in increasing PRA levels and that replacing REM sleep by waking periods and light sleep does not modify nocturnal PRA oscillations.