6 research outputs found
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
BackgroundShortened rapid eye movement (REM) sleep latency and increased REM sleep amount are presumed biological markers of depression. These sleep alterations are also observable in several animal models of depression as well as during the rebound sleep after selective REM sleep deprivation (RD). Furthermore, REM sleep fragmentation is typically associated with stress procedures and anxiety. The selective serotonin reuptake inhibitor (SSRI) antidepressants reduce REM sleep time and increase REM latency after acute dosing in normal condition and even during REM rebound following RD. However, their therapeutic outcome evolves only after weeks of treatment, and the effects of chronic treatment in REM-deprived animals have not been studied yet.ResultsChronic escitalopram- (10 mg/kg/day, osmotic minipump for 24 days) or vehicle-treated rats were subjected to a 3-day-long RD on day 21 using the flower pot procedure or kept in home cage. On day 24, fronto-parietal electroencephalogram, electromyogram and motility were recorded in the first 2 h of the passive phase. The observed sleep patterns were characterized applying standard sleep metrics, by modelling the transitions between sleep phases using Markov chains and by spectral analysis.Based on Markov chain analysis, chronic escitalopram treatment attenuated the REM sleep fragmentation [accelerated transition rates between REM and non-REM (NREM) stages, decreased REM sleep residence time between two transitions] during the rebound sleep. Additionally, the antidepressant avoided the frequent awakenings during the first 30 min of recovery period. The spectral analysis showed that the SSRI prevented the RD-caused elevation in theta (5 inverted question mark9 Hz) power during slow-wave sleep. Conversely, based on the aggregate sleep metrics, escitalopram had only moderate effects and it did not significantly attenuate the REM rebound after RD.ConclusionIn conclusion, chronic SSRI treatment is capable of reducing several effects on sleep which might be the consequence of the sub-chronic stress caused by the flower pot method. These data might support the antidepressant activity of SSRIs, and may allude that investigating the rebound period following the flower pot protocol could be useful to detect antidepressant drug response. Markov analysis is a suitable method to study the sleep pattern
Nesfatin-1/NUCB2 as a Potential New Element of Sleep Regulation in Rats.
STUDY OBJECTIVES: Millions suffer from sleep disorders that often accompany severe illnesses such as major depression; a leading psychiatric disorder characterized by appetite and rapid eye movement sleep (REMS) abnormalities. Melanin-concentrating hormone (MCH) and nesfatin-1/NUCB2 (nesfatin) are strongly co - expressed in the hypothalamus and are involved both in food intake regulation and depression. Since MCH was recognized earlier as a hypnogenic factor, we analyzed the potential role of nesfatin on vigilance. DESIGN: We subjected rats to a 72 h-long REMS deprivation using the classic flower pot method, followed by a 3 h-long 'rebound sleep'. Nesfatin mRNA and protein expressions as well as neuronal activity (Fos) were measured by quantitative in situ hybridization technique, ELISA and immunohistochemistry, respectively, in 'deprived' and 'rebound' groups, relative to controls sacrificed at the same time. We also analyzed electroencephalogram of rats treated by intracerebroventricularly administered nesfatin-1, or saline. RESULTS: REMS deprivation downregulated the expression of nesfatin (mRNA and protein), however, enhanced REMS during 'rebound' reversed this to control levels. Additionally, increased transcriptional activity (Fos) was demonstrated in nesfatin neurons during 'rebound'. Centrally administered nesfatin-1 at light on reduced REMS and intermediate stage of sleep, while increased passive wake for several hours and also caused a short-term increase in light slow wave sleep. CONCLUSIONS: The data designate nesfatin as a potential new factor in sleep regulation, which fact can also be relevant in the better understanding of the role of nesfatin in the pathomechanism of depression
Differential adaptation of REM sleep latency, intermediate stage and theta power effects of escitalopram after chronic treatment.
The effects of the widely used selective serotonin reuptake
inhibitor (SSRI) antidepressants on sleep have been intensively
investigated. However, only a few animal studies examined the
effect of escitalopram, the more potent S-enantiomer of
citalopram, and conclusions of these studies on sleep
architecture are limited due to the experimental design. Here,
we investigate the acute (2 and 10 mg/kg, i.p. injected at the
beginning of the passive phase) or chronic (10 mg/kg/day for 21
days, by osmotic minipumps) effects of escitalopram on the sleep
and quantitative electroencephalogram (EEG) of Wistar rats. The
first 3 h of EEG recording was analyzed at the beginning of
passive phase, immediately after injections. The acutely
injected 2 and 10 mg/kg and the chronically administered 10
mg/kg/day escitalopram caused an approximately three, six and
twofold increases in rapid eye movement sleep (REMS) latency,
respectively. Acute 2-mg/kg escitalopram reduced REMS, but
increased intermediate stage of sleep (IS) while the 10 mg/kg
reduced both. We also observed some increase in light slow wave
sleep and passive wake parallel with a decrease in deep slow
wave sleep and theta power in both active wake and REMS after
acute dosing. Following chronic treatment, only the increase in
REMS latency remained significant compared to control animals.
In conclusion, adaptive changes in the effects of escitalopram,
which occur after 3 weeks of treatment, suggest desensitization
in the function of 5-HT(1A) and 5-HT(1B) receptors
Opposing local effects of endocannabinoids on the activity of noradrenergic neurons and release of noradrenaline: relevance for their role in depression and in the actions of CB(1) receptor antagonists.
There is strong evidence that endocannabinoids
modulate signaling of serotonin and noradrenaline, which
play key roles in the pathophysiology and treatment of
anxiety and depression. Most pharmacological and genetic,
human and rodent studies suggest that the presence of
under-functioning endocannabinoid type-1 (CB1) receptors
is associated with increased anxiety and elevated extracellular
serotonin concentration. In contrast, noradrenaline
is presumably implicated in the mediation of depressiontype
symptoms of CB1 receptor antagonists. Evidence
shows that most CB1 receptors located on axons and
terminals of GABA-ergic, serotonergic or glutamatergic
neurons stimulate the activity of noradrenergic neurons.
In contrast, those located on noradrenergic axons and
terminals inhibit noradrenaline release efficiently. In this
latter process, excitatory ionotropic or G protein-coupled
receptors, such as the NMDA, alpha1 and beta1 adrenergic
receptors, activate local endocannabinoid synthesis at
postsynaptic sites and stimulate retrograde endocannabinoid
neurotransmission acting on CB1 receptors of noradrenergic
terminals. The underlying mechanisms include
calcium signal generation, which activates enzymes that
increase the synthesis of both anandamide and 2-
arachidonoylglycerol,
while Gq/11 protein activation also increases
the formation of 2-arachidonoylglycerol from
diacylglycerol during the signaling process. In addition,
other non-CB1 receptor endocannabinoid targets such as
CB2, transient receptor potential vanilloid subtype, peroxisome
proliferator-activated receptor-alpha and possibly
GPR55 can also mediate some of the endocannabinoid
effects. In conclusion, both neuronal activation and
neurotransmitter
release depend on the in situ synthesized
endocannabinoids and thus, local endocannabinoid concentrations
in different brain areas may be crucial in the net
effect, namely in the regulation of neurons located
postsynaptically
to the noradrenergic synapse