Acute escitalopram treatment inhibits REM sleep rebound and activation of MCH-expressing neurons in the lateral hypothalamus after long term selective REM sleep deprivation

Abstract

Rationale Selective rapid eye movement sleep (REMS) deprivation using the platform-on-water ("flower pot") method causes sleep rebound with increased REMS, decreased REMS latency, and activation of the melaninconcentrating hormone (MCH) expressing neurons in the hypothalamus. MCH is implicated in the pathomechanism of depression regarding its influence on mood, feeding behavior, and REMS. Objectives We investigated the effects of the most selective serotonin reuptake inhibitor escitalopram on sleep rebound following REMS deprivation and, in parallel, on the activation of MCH-containing neurons.Methods Escitalopram or vehicle (10 mg/kg, intraperitoneally) was administered to REMS-deprived (72 h) or home cage male Wistar rats. During the 3-h-long "rebound sleep", electroencephalography was recorded, followed by an MCH/Fos double immunohistochemistry. Results During REMS rebound, the time spent in REMS and the number of MCH/Fos double-labeled neurons in the lateral hypothalamus increased markedly, and REMS latency showed a significant decrease. All these effects of REMS deprivation were significantly attenuated by escitalopram treatment. Besides the REMS-suppressing effects, escitalopram caused an increase in amount of and decrease in latency of slow wave sleep during the rebound. Conclusions These results show that despite the high REMS pressure caused by REMS deprivation procedure, escitalopram has the ability to suppress REMS rebound, as well as to diminish the activation of MCH-containing neurons, in parallel. Escitalopram caused a shift from REMS to slow wave sleep during the rebound. Furthermore, these data point to the potential connection between the serotonergic system and MCH in sleep regulation, which can be relevant in depression and in other mood disorders.

Chronic escitalopram treatment attenuated the accelerated rapid eye movement sleep transitions after selective rapid eye movement sleep deprivation: a model-based analysis using Markov chains

“…Based on the aggregate sleep measures (Table 3 ), we did not find any changes denoting enhanced wake pressure or sleep fragmentation after RD, which is consistent with previous reports [ 11 , 12 , 76 ].…”

“…Furthermore, stress could be a main factor also in the suppression of NREM sleep [ 58 – 60 ]. Some studies have revealed also an enhancement in REM episode duration (in the first 3 h [ 12 ] and 2–24 h of the recovery period after 72 h RD [ 11 ]; in the first 6 h after 2 days of 18 h RD [ 56 ]). However, we did not find here an enhanced REM duration after RD; in fact, there was a tendency to decrease regarding this parameter.…”

“…Furthermore, we cannot neglect the possibility that the time interval examined here might be too short to manifest marginal effects of RD on REM duration. Another possible cause of this discrepancy could be that in some studies short REM attempts (a period of REM sleep lasting for ≥16 s and not interrupted by ≥16 s of other vigilance state) were excluded from REM sleep episodes [ 11 , 12 ]. So, we evaluated our data also according to the definition above and we found the similar effect of RD on REM duration, but it was only a tendency to increase (data not shown).…”

“…We reported earlier that acute escitalopram administration (10 mg/kg, i.p.) in rats immediately after the same RD protocol attenuated the REM sleep rebound (decreased time spent in REM and REM number, increased REM latency) during the first 3 h of recovery sleep [ 12 ]. These results provided evidence that acute escitalopram is still able to reduce REM sleep despite the strong REM pressure.…”

Escitalopram affects spexin expression in the rat hypothalamus, hippocampus and striatum

“…On the other hand, escitalopram has the ability to diminish the activation of hypothalamic neurons containing melanin concentrating hormone (MCH) and to suppress REM sleep rebound [30]. The potential interplay between SPX and MCH signalling is so far unknown, however it is worth noting that escitalopram may inhibit the action of another regulatory neuropeptide in the hypothalamus.…”