REM Sleep Deprived Rats Research Articles

Crocin (bioactive compound of Crocus sativus L.) potently restores REM sleep deprivation-induced manic- and obsessive-compulsive-like behaviors in female rats.

Rapid-eye movement (REM) sleep deprivation (SD) can induce manic-like behaviors including hyperlocomotion. On the other hand, crocin (one of the main compounds of Crocus sativus L. or Saffron) may be beneficial in the improvement of mental and cognitive dysfunctions. Also, crocin can restore the deleterious effects of SD on mental and cognitive processes. In this study, we investigated the effect of REM SD on female rats' behaviors including depression- and anxiety-like behaviors, locomotion, pain perception, and obsessive-compulsive-like behavior, and also, the potential effect of crocin on REM SD effects. We used female rats because evidence on the role of REM SD in modulating psychological and behavioral functions of female (but not male) rats is limited. REM SD was induced for 14 days (6h/day), and crocin (25, 50, and 75 mg/kg) was injected intraperitoneally. Open field test, forced swim test, hot plate test, and marble burying test were used to assess rats' behaviors. The results showed REM SD-induced manic-like behavior (hyperlocomotion). Also, REM SD rats showed decreased anxiety- and depression-like behavior, pain subthreshold (the duration it takes for the rat to feel pain), and showed obsessive compulsive-like behavior. However, crocin at all doses partially or fully reversed REM SD-induced behavioral changes. In conclusion, our results suggested the possible comorbidity of OCD and REM SD-induced manic-like behavior in female rats or the potential role of REM SD in the etiology of OCD, although more studies are needed. In contrast, crocin can be a possible therapeutic choice for decreasing manic-like behaviors.

Impact of endogenous analgesia triggered by acupuncture, stress, or noxious stimulation on REM sleep-deprived rats.

Poor sleep increases pain, at least in part, by disrupting endogenous pain modulation. However, the efficacy of endogenous analgesia in sleep-deprived subjects has never been tested. To assess this issue, we chose three different ways of triggering endogenous analgesia: (1) acupuncture, (2) acute stress, and (3) noxious stimulation, and compared their ability to decrease the pronociceptive effect induced by REM-SD (Rapid Eye Movement Sleep Deprivation) with that to decrease inflammatory hyperalgesia in the classical carrageenan model. First, we tested the ability of REM-SD to worsen carrageenan-induced hyperalgesia: Alow dose of carrageenan (30 µg) in sleep-deprived Wistar rats resulted in a potentiated hyperalgesic effectthat was more intense and longer-lasting than that induced by a higher standard dose of carrageenan (100 µg) or by REM-SD alone. Then, we found that (1) acupuncture, performed at ST36, completely reversed the pronociceptive effect induced by REM-SD or by carrageenan; (2) immobilization stress completely reversed the pronociceptive effect of REM-SD, while transiently inhibited carrageenan-induced hyperalgesia; (3) noxious stimulation of the forepaw by capsaicin also reversed the pronociceptive effect of REM-SD and persistently increased the nociceptive threshold above the baseline in carrageenan-treated animals. Therefore, acupuncture, stress, or noxious stimulation reversed the pronociceptive effect of REM-SD, while each intervention affected carrageenan-induced hyperalgesia differently. This study has shown that while sleep loss may disrupt endogenous pain modulation mechanisms, it does not prevent theactivation of these mechanisms to induce analgesia in sleep-deprived individuals.

Chronic REM sleep deprivation leads to manic- and OCD-related behaviors, and decreases hippocampal BDNF expression in female rats.

Rapid-eye movement (REM) sleep deprivation (SD) can induce manic-like behaviors in rodents. On the other hand, lithium, as one of the oldest drugs used in neuropsychiatric disorders, is still one of the best drugs for the treatment and control of bipolar disorder. In this study, we aimed to investigate the role of chronic short-term REM SD in the induction of manic-like behaviors in female rats. The rats were exposed to REM SD for 14 days (6 hours/day). Lithium was intraperitoneally injected at the doses of 10, 50, and 100 mg/kg. REM SD induced hyperactivity and OCD-like behavior, and decreased anxiety, depressive-like behavior, and pain subthreshold. REM SD also impaired passive avoidance memory and decreased hippocampal brain-derived neurotrophic factor (BDNF) expression level. Lithium at the doses of 50 and 100 mg/kg partly and completely abolished these effects, respectively. However, lithium (100 mg/kg) increased BDNF expression level in control and sham REM SD rats with no significant changes in behavior. Chronic short-term REM SD may induce a mania-like model and lead to OCD-like behavior and irritability. In the present study, we demonstrated a putative rodent model of mania induced by chronic REM SD in female rats. We suggest that future studies should examine behavioral and mood changes following chronic REM SD in both sexes. Furthermore, the relationship between manic-like behaviors and chronic REM SD should be investigated.

Cognitive Enhancing Activities of Coenzyme Q10, Ramipril, and Vinpocetine Through Modulating Neuroinflammatory Response and Oxidative Damage Inflicted by Acute REM Sleep Deprivation in Rats

Sleep plays a vital role to help in normal biological functions that are required for normal cognitive functioning. This study was done to determine the cognition-modulating effects of coenzyme Q10 (CoQ10), ramipril, and vinpocetine on REM sleep-deprived acute insomniac rat models. A total of Forty-eight albino rats were divided into eight groups (Gr) (n=6).). Gr. 1 was REM control and Gr. 2 was REM sleep-deprived rats treated with water. Gr. 3 to Gr.8 - REM sleep-deprived rats were administered corn oil, donepezil, vinpocetine, coenzyme Q10+corn oil, ramipril, and (coenzyme Q10 + corn oil + ramipril) respectively. Except for the control Gr 1, REM sleep deprivation was induced in Gr. 2 and 8 daily for 7 days. All the rats were subjected to a Morris water maze (MWM) to test the navigation memory dysfunction after 7 days of acute insomnia. The rats were deprived of REM sleep by using a modified multiple platform method. The body weight of the animals was measured on day 1 and day 7. On day 1 and Day 2 acquisition trials, all groups of rats showed comparable latency time required to reach the hidden platform. However, on day 3 and Day 4, rats treated with coenzyme Q10, ramipril, and the combination (CoQ10+ Ramipril) showed a significant decrease in latency time (p<0.01). In the probe trial, sleep-deprived rats showed a significant decrease (p<0.001) in the percentage of time spent in the target quadrant as compared to the REM control. However, there was a significant increase in the percentage time spent in CoQ10, ramipril, the combination (CoQ10+ ramipril), donepezil, and vinpocetine as compared to sleep-deprived rats (p<0.05). At the end of day 7 of insomnia, when the body weight of rats was compared with day 1, there was a significant decrease in weight gain was seen with the sleep-deprived rats treated with corn oil, ramipril, vinpocetine, CoQ10, and (CoQ10+ramipril) (p<0.05). The present study shows that coenzyme Q10, ramipril, and their combination improve sleep deprivation induced cognition impairment.

Downregulation of microRNA-330-5p induces manic-like behaviors in REM sleep-deprived rats by enhancing tyrosine hydroxylase expression.

In our pilot study, we found an increase in tyrosine hydroxylase (Th) mRNA expression in the prefrontal cortex of 72-h REM sleep-deprived (SD) rats, a mania model. Additionally, the expression levels of miR-325-3p, miR-326-3p, and miR-330-5p, the predicted target miRNAs on TH, were significantly decreased. Based on these results, in this study, we investigated whether miRNA-325-3p, miR-326-3p, and miR-330-5p modulate TH and manic-like behaviors in SD rats. Manic-like behaviors were assessed using the open field test (OFT) and elevated plus-maze (EPM) test. The direct binding activity of miRNAs to the 3'-untranslated region (3'-UTR) of the Th gene was measured in HEK-293 cells using a luciferase reporter system. We also examined mRNA and protein expression of TH after intracerebroventricular (ICV) injection of miR-330-5p agomir to SD rats, along with manic-like behaviors. We observed an upregulation in mRNA and protein expression of TH and downregulation in miRNA-325-3p, miR-326-3p, and miR-330-5p expressions in the prefrontal cortex of SD rats, together with increased manic-like behaviors. The luciferase reporter assay showed that miR-330-5p could repress TH expression through direct binding to its target site in the 3'-UTR of Th, whereas miR-326-3p and miR-330-5p could not. In addition, ICV injection of miR-330-5p agomir alleviated the increase in TH expression in the prefrontal cortex of SD rats and manic-like behaviors. TH expression regulation through miR-330-5p may be implicated in the pathophysiology of mania in SD rats.

Gastrodin Improves Cognitive Dysfunction in REM Sleep-Deprived Rats by Regulating TLR4/NF-κB and Wnt/β-Catenin Signaling Pathways

Gastrodin is the active ingredient in Gastrodia elata. Our previous studies demonstrated that gastrodin ameliorated cerebral ischemia-reperfusion and hypoperfusion injury and improved cognitive deficit in Alzheimer's disease. This study aims to examine the effects of gastrodin on REM sleep deprivation in rats. Gastrodin (100 and 150 mg/kg) was orally administered for 7 consecutive days before REM sleep deprivation. Seventy-two hours later, pentobarbital-induced sleep tests and a Morris water maze were performed to measure REM sleep quality and learning and memory ability. Histopathology was observed with hematoxylin-eosin staining, and the expression of the NF-κB and Wnt/β-catenin signaling pathways was examined using Western blot. After REM sleep deprivation, sleep latency increased and sleep duration decreased, and the ability of learning and memory was impaired. Neurons in the hippocampal CA1 region and the cortex were damaged. Gastrodin treatment significantly improved REM sleep-deprivation-induced sleep disturbance, cognitive deficits and neuron damage in the hippocampus CA1 region and cerebral cortex. A mechanism analysis revealed that the NF-κB pathway was activated and the Wnt/β-catenin pathway was inhibited after REM sleep deprivation, and gastrodin ameliorated these aberrant changes. Gastrodin improves REM sleep-deprivation-induced sleep disturbance and cognitive dysfunction by regulating the TLR4/NF-κB and Wnt/β-catenin signaling pathways and can be considered a potential candidate for the treatment of REM sleep deprivation.

Oxidative Stress Induces Endothelial Dysfunction and Endothelial Cell Damage in Rapid Eye Movement (REM) Sleep Deprivation Animal Model

INTRODUCTION: Rapid eye movement (REM) sleep deprivation causes oxidative stress, leading to endothelial dysfunction, a predictor of cardiovascular disease. It is still unclear what causes endothelial dysfunction in patients with sleep disorder. This study evaluates the effects of REM sleep deprivation on the endothelium in the rat model of REM sleep deprivation. MATERIALS AND METHODS: Sprague-Dawley male rats (N=28) were divided into four groups (n=7); (1) free-moving control (FMC), (2) REM sleep deprivation (REMsd), (3) tank control (TC), and (4) sleep recovery (SR). The inverted flowerpot technique was utilised to develop REM sleep deprivation. Bodyweight gain (BWg), food consumption (Fc), and systolic blood pressure (SBP) were evaluated. The descending thoracic aorta was isolated to assess oxidative stress markers, in vitro functional study, and histomorphological examination. RESULTS: REM sleep deprivation showed a decrease in BWg significantly despite a significant increase in Fc, increased SBP, increased oxidative stress markers, caused endothelial dysfunction and endothelial cell damage. In REM sleep-deprived rats, there was a significant reduction in antioxidant markers, including total antioxidant capacity (TAC), superoxide dismutase (SOD) activity, catalase (CAT), and glutathione (GSH), while the levels of malondialdehyde (MDA) were significantly increased. The REM sleep-deprived rats displayed altered vascular function, including impaired vasorelaxation and hypercontractility. Histomorphology of the endothelium in REM sleep-deprived rats revealed features of endothelial damage. CONCLUSION: REM sleep deprivation is suggested to be linked to endothelial dysfunction due to endothelial damage. These changes are proposed to result from increased oxidative stress. Sleep recovery reduced the harmful effects following REM sleep deprivation.

Lithium Treatment Improves Cardiac Dysfunction in Rats Deprived of Rapid Eye Movement Sleep.

Rapid eye movement (REM) sleep deprivation triggers mania and induces cardiac fibrosis. Beyond neuroprotection, lithium has cardioprotective potential and antifibrotic activity. This study investigated whether lithium improved REM sleep deprivation-induced cardiac dysfunction and evaluated the potential mechanisms. Transthoracic echocardiography, histopathological analysis, and Western blot analysis were performed in control and REM sleep-deprived rats with or without lithium treatment (LiCl of 1 mmol/kg/day administered by oral gavage for 4 weeks) in vivo and in isolated ventricular preparations. The results revealed that REM sleep-deprived rats exhibited impaired contractility and greater fibrosis than control and lithium-treated REM sleep-deprived rats. Western blot analysis showed that REM sleep-deprived hearts had higher expression levels of transforming growth factor beta (TGF-β), phosphorylated Smad 2/3, and alpha-smooth muscle actin than lithium-treated REM sleep-deprived and control hearts. Moreover, lithium-treated REM sleep-deprived hearts had lower expression of angiotensin II type 1 receptor, phosphorylated nuclear factor kappa B p65, calcium release-activated calcium channel protein 1, transient receptor potential canonical (TRPC) 1, and TRPC3 than REM sleep-deprived hearts. The findings suggest that lithium attenuates REM sleep deprivation-induced cardiac fibrogenesis and dysfunction possibly through the downregulation of TGF-β, angiotensin II, and Ca2+ signaling.

Effects of uridine administration on hippocampal matrix metalloproteinases and their endogenous inhibitors in REM sleep-deprived rats

Rapid eye movement (REM) sleep is associated with synaptic plasticity which is considered essential for long-term potentiation (LTP). The composition of extracellular matrix (ECM), in part, plays a role in REM sleep-associated synaptic functioning. The objective of this study was to investigate the effects of uridine administration on levels of matrix metalloproteinases (MMPs) and their endogenous inhibitors (TIMPs) in rats subjected to REM sleep deprivation (REMSD). REMSD was induced by modified multiple platform method for 96-hour. Rats were randomized to receive either saline or uridine (1 mmol/kg) intraperitoneally twice a day for four days. Rats were then decapitated and their hippocampi were dissected for analyzing the levels of MMP-2, MMP-3, MMP-9, TIMP-1, TIMP-2 and TIMP-3 by Western-blotting and the activities of MMP-2 and MMP-9 by Gelatin zymography. REMSD resulted in reduced levels of MMP-3, MMP-9, TIMP-3 and activity of MMP-9 in saline-treated rats, while uridine treatment significantly enhanced their impairment. TIMP-1 was enhanced following REMSD but uridine treatment had no significant effect on TIMP-1 levels. MMP-2, TIMP-2 levels and MMP-2 activity were not affected by either REMSD or uridine administration. These data show that REMSD significantly affects ECM composition which is ameliorated by uridine administration suggesting a possible use of uridine in sleep disorders.

Effects of citicoline administration on synaptic proteins in rapid eye movement sleep-deprived rats.

Objective(s):Sleep has a pivotal role in learning-memory and sleep deprivation (SD) negatively affects synaptic functioning. Cytidine-5-diphosphocholine (Citicoline) has been known to improve learning and memory functions. Our objective was to explore the effects of Citicoline on hippocampal and cortical synaptic proteins in rapid eye movement (REM) sleep-deprived rats.Materials and Methods:Rats (n=36) were randomly divided into 6 groups. Environmental control or sleep deprivation was done by placing the rat on a 13 cm diameter platform (Large Platform [LP] group) or on a 6.5 cm diameter platform (REMSD group), respectively, for 96 hours. Rats randomized for controls (Home Cage [HC] group) were followed up in home cages. Rats in each of the REMSD, LP or HC group were randomized to receive either saline (0,9%NaCl) or Citicoline (600 μmol/kg) intraperitoneally twice a day for four days. After the experiments, rats were sacrificed; their cerebral cortices and hippocampi were dissected for analyzing the levels of pre-synaptic proteins synaptophysin and synapsin I, and the post-synaptic density protein-95 (PSD-95) by Western-blotting. Results: Hippocampal levels of PSD-95, but not the pre-synaptic proteins, were reduced by REM sleep deprivation. Citicoline treatment ameliorated the reduction in PSD-95 levels in REM sleep-deprived rats. On the other hand, REM sleep deprivation was not found to be significantly effective on pre- or post-synaptic proteins in cerebral cortex.Conclusion:REM sleep deprivation reduces hippocampal PSD-95 levels which are enhanced by Citicoline treatment. These data propose that Citicoline may ameliorate the adverse effects of SD on hippocampal synaptic functioning.

Effects of citicoline administration on synaptic proteins in rapid eye movement sleep-deprived rats

Effects of citicoline administration on synaptic proteins in rapid eye movement sleep-deprived rats

Impact of Rapid Eye Movement Sleep Deprivation on Pain Behaviour and Oxidative Stress in the Thalamus: Role of Tualang Honey Supplementation.

BackgroundInsufficient sleep alters the body’s physiological functions. This study investigated whether oxidative stress (OS) in the thalamus was correlated with the pain behaviour score in the rapid eye movement (REM) sleep-deprived rat model.MethodsFour groups of Sprague-Dawley rats were included in the study (n = 6): i) control; ii) REM sleep-deprived rats for 72 h (REMsd); iii) REM sleep-deprived rats for 72 h pretreated with Tualang honey (REMsd-H) and iv) tank control (TC). Following the intervention, 1% formalin was injected on the right hind paw and pain behaviour was recorded for 1 h. OS markers of glutathione (GSH), glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) in the thalamus were measured.ResultsREM sleep deprivation increased pain behaviour scores in phase II of the formalin test with decreased GSH, GR, SOD and CAT. The MDA level was significantly higher in the REMsd compared to REMsd-H. There was an inverse correlation between pain behaviour scores and GSH, GR and SOD levels. A positive correlation was found between the pain behaviour score and the MDA level.ConclusionOS levels were significantly correlated with the pain behaviour score in the REMsd rats. Tualang honey administration reduced pain behaviour score and OS in the thalamus.

Electrophysiological and neurochemical evaluation of the adverse effects of REM sleep deprivation and epileptic seizures on rat's brain

AimThe current study aims to investigate the impact of paradoxical (REM) sleep deprivation and/or epileptic seizures on rat's cortical brain tissues. Main methodsAnimals were divided into four groups; control, epileptic, REM sleep deprived and epileptic subjected to REM sleep deprivation. Electrocorticogram (ECoG) signals were recorded and quantitatively analyzed for each group. Concentrations of amino acid neurotransmitters; proinflammatory cytokines; and oxidative stress parameters; and acetylcholinesterase activity were determined in the cortex of the animals in different groups. Key findingsResults showed significant variations in the spectral distribution of ECoG waves in the epilepsy model, 24- and 48-hours of REM sleep deprivation and their combined effects indicating a state of cortical hyperexcitability. Significant increases in NO and taurine and significant decrement in glutamine, GABA and glycine were determined. In REM sleep deprived rats significant elevation in glutamate, aspartate, glycine and taurine and a significant lowering in GABA were obtained. This was accompanied by significant reduction in AchE and IL-β. In the cortical tissue of epileptic rats deprived from REM sleep significant increases in lipid peroxidation, TNF-α, IL-1β, IL-6 and aspartate and a significant reduction in AchE were observed. SignificanceThe present data indicate that REM sleep deprivation induces an increase in lipid peroxidation and storming in proinflammatory cytokines in the cortex of rat model of epilepsy during SRS. These changes are associated with a decreased seizure threshold as inferred from the increase in alpha and Beta waves and a decrease in Delta waves of ECoG.

The effect of alpha lipoic acid on passive avoidance and social interaction memory, pain perception, and locomotor activity in REM sleep-deprived rats.

Evidence shows the vital role of sleep in the modulation of cognitive functions. Sleep deprivation (SD) can disrupt learning and memory processes. SD also affects pain perception and locomotor activity. Furthermore, alpha lipoic acid (ALA) may induce antioxidant and neuroprotective effects. ALA affects memory processes, pain subthreshold, and locomotor activity. The goal of the present study was to investigate the effect of REM (rapid-eye movement) SD and ALA on social and passive avoidance memory, locomotor activity, and pain perception. Multiple-platform apparatus was used to induce REM SD for 24h. Three-chamber paradigm test, the shuttle box, locomotion apparatus, and hot plate were used to assess social interaction memory, passive avoidance memory, locomotor activity, and pain perception, respectively. ALA was injected intraperitoneally at the doses of 35 and 70mg/kg. 24h REM SD impaired both types of memory. In addition, ALA (35mg/kg) reversed REM SD-induced memory impairments. However, ALA (70mg/kg) impaired social memory with no effect on REM SD-induced memory impairments. ALA (70mg/kg) also decreased pain subthreshold in REM SD rats. REM SD impairs social interaction and passive avoidance memory. Furthermore, ALA may exhibit a dose-dependent manner in some cognitive tasks. ALA can induce a therapeutic effect at one dose, and an impairment effect at another dose (lower or higher), while the cognitive task and the conditions are equal.

Novel object recognition memory in REM sleep-deprived rats: Role of the cannabinoid CB1 receptor

A survey of the literature indicates that both rapid eye movement sleep deprivation (RSD) and activation of cannabinoid CB1 receptor (CB1R) may impair novel object recognition (NOR) memory in rodents. To our knowledge, so far, no previous study has investigated the probable effects of RSD on the different phases of NOR memory. Moreover, far too little attention has been paid to the potential role of the CB1R in the effects of RSD on object memory. Therefore, the major objective of this study was to investigate the probable role of the CB1R in the acquisition, consolidation, retrieval, and reconsolidation of NOR memory in the RSD rats. A 12-h paradigm of RSD using the multiple platform method did not affect acquisition, but it impaired the consolidation, retrieval, and reconsolidation of NOR memory. Administration of the CB1R antagonist rimonabant (1 or 3 mg/kg, i.p.) did not have significant effects on the acquisition and reconsolidation, but it improved RSD-induced impairment of the consolidation and retrieval of object memory, especially at the dose of 3 mg/kg. In addition, the RSD paradigm did not affect the levels of plasma corticosterone as an important marker of stress in rat. The results revealed that RSD may have different effects on the different phases of NOR memory which may not be attributable to the effects of stress. Our findings would seem to suggest that the CB1R can be targeted to, at least partially, modulate the adverse effects of RSD on the process of NOR memory.

Caffeine as a potential arousal enhancer: altered NMDA subunit gene expression without improving cognitive performance in REM sleep deprived rats

Caffeine is one of the most extensively consumed stimulants in the world and has been suggested to induce wakefulness by antagonizing the function of the adenosine A2A receptor. Therefore, we investigated the effects of chronic caffeine consumption on learning and memory in the REM sleep-deprived rats.Male Wistar rats (n = 50), were randomly assigned into 5 groups: Control (C), Caffeine (Cf), Pedestal Control (PC), Sleep Deprivation (SD), Sleep Deprivation and Caffeine (SD + Cf). Sleep deprivation procedure was applied as the flower-pot technique. SD and SD + Cf groups were deprived for 18 hours in a day for 21 days. Caffeine was administered daily in drinking water (0.3 g⁄L) for 5 weeks. For evaluated learning and memory function, Morris Water Maze Test (MWM) was used. Fluidigm Access Array was used for Grin2a, Grin2b, BDNF, cdk5/cdk5r1, CaMKIIa genes expression in the hippocampus. Distance moved and escape latency were decreased through trial days (p<0.05). However, there is no significant difference between groups for time spent in targeted quadrant during probe test for memory performance. Grin2a up-regulation was found in Cf and SD+Cf (p<0.05), and cdk5r1 increased in Cf and PC control (p<0.05). Also, BDNF up-regulation was found in PC group. Grin2b, Cdk5, CaMKIIa expression levels were not changed significantly. We showed chronic caffeine altered some of the hippocampal genes without changing learning and memory in REM sleep deprived rats. Chronic consumption of caffeine caused up-regulation in Grin2a that subunit of NMDA receptor. We supposed that chronic caffeine consumption maintained arousal without affecting learning and memory performance.

Cannabidiol modulates the expression of neuroinflammatory factors in stress- and drug-induced reinstatement of methamphetamine in extinguished rats.

Methamphetamine (METH) is a highly potent and addictive psychostimulant that is frequently abused worldwide. Although the biggest challenge to the efficient treatment of drug dependence is relapse, its mechanism is completely unclear. Plenty of evidence suggests that inflammation contributes to drug-induced reward especially in brain regions that are involved in the reward system, but there is no document about relapse. Cannabidiol (CBD) is a nonpsychoactive cannabinoid that has powerful anti-inflammatory and immunosuppressive properties. A previous research in our laboratory has demonstrated that CBD prevents reinstatement of METH even in 24-hour rapid eye movement (REM) sleep-deprived (RSD) rats. The aim of this study was to assess whether CBD prevents reinstatement of METH through change of gene expression of cytokines such as interleukin-1β, interleukin-6, interleukin-10, and tumor necrosis factor α (TNF-α) in extinguished rats. Real-time polymerase chain reaction (PCR) was used in this research to assay gene expression of cytokines. We found that stress- and drug-induced reinstatement of METH enhanced mRNA expression of cytokines in the prefrontal cortex (PFC) and hippocampus. Furthermore, CBD treatment significantly reduced the mRNA expression of cytokines in the PFC and hippocampus, but CBD treatment in RSD rats increased expression of cytokines in the hippocampus. It seems that enhancement of cytokines leads to change in neurotransmission and so triggers reinstatement of METH.

Noradrenaline Acting on Alpha1 Adrenoceptor as well as by Chelating Iron Reduces Oxidative Burden on the Brain: Implications With Rapid Eye Movement Sleep.

The noradrenaline (NA) level in the brain is reduced during rapid eye movement sleep (REMS). However, upon REMS deprivation (REMSD) its level is elevated, which induces apoptosis and the degeneration of neurons in the brain. In contrast, isolated studies have reported that NA possesses an anti-oxidant property, while REMSD reduces lipid peroxidation (LP) and reactive oxygen species (ROS). We argued that an optimum level of NA is likely to play a physiologically beneficial role. To resolve the contradiction and for a better understanding of the role of NA in the brain, we estimated LP and ROS levels in synaptosomes prepared from the brains of control and REMS deprived rats with or without in vivo treatment with either α1-adrenoceptor (AR) antagonist, prazosin (PRZ) or α2-AR agonist, clonidine (CLN). REMSD significantly reduced LP and ROS in synaptosomes; while the effect on LP was ameliorated by both PRZ and CLN; ROS was prevented by CLN only. Thereafter, we evaluated in vitro the effects of NA, vitamin E (Vit E), vitamin C (Vit C), and desferrioxamine (DFX, iron chelator) in modulating hydrogen peroxide (H2O2)-induced LP and ROS in rat brain synaptosomes, Neuro2a, and C6 cells. We observed that NA prevented ROS generation by chelating iron (inhibiting a Fenton reaction). Also, interestingly, a lower dose of NA protected the neurons and glia, while a higher dose damaged the neurons and glia. These in vitro and in vivo results are complementary and support our contention. Based on the findings, we propose that REMS maintains an optimum level of NA in the brain (an antioxidant compromised organ) to protect the latter from continuous oxidative onslaught.

Uridine treatment prevents REM sleep deprivation-induced learning and memory impairment

Previous studies have shown that sleep plays an important role in cognitive functions and sleep deprivation impairs learning and memory. Uridine is the main pyrimidine nucleoside found in human blood circulation and has beneficial effects on cognitive functions. The aim of the present study was to investigate the effects of uridine administration on learning and memory impairment in sleep-deprived rats. Flower pot method was used to induce REM sleep deprivation. Uridine-treated groups received 1 mmol/kg uridine and control groups received 1 ml/kg saline (0.9% NaCl) twice a day for four days and once a day on the 5th day intraperitoneally. Learning and memory performances were measured using Morris water maze (MWM) test. We also measured the ratios of total calcium-calmodulin dependent kinase II (tCaMKII)/β-tubulin and phosphorylated cyclic adenosine monophosphate (cAMP) response element binding protein (pCREB)/β-tubulin, long-term potentiation (LTP) related molecules, using western blot analysis on the hippocampus. The results showed that REM sleep deprivation impaired learning and memory and also decreased the ratios of tCaMKII and pCREB. Uridine treatment enhanced learning and memory parameters in REM sleep-deprived rats. Additionally, decreases in tCaMKII and pCREB were prevented by uridine treatment. These data suggest that administration of uridine for five consecutive days prevents REM sleep deprivation-induced deficits in learning and memory associated with enhanced tCaMKII and pCREB ratios in the hippocampus.

Role of Cannabinoid CB1, Receptor in Object Recognition Memory Impairment in Chronically Rapid Eye Movement Sleep-deprived Rats

ObjectiveWe aimed to investigate whether antagonism of the cannabinoid CB1 receptor (CB1R) could affect novel object recognition (NOR) memory in chronically rapid eye movement sleep-deprived (RSD) rats. MethodsThe animals were examined for recognition memory following a 7-day chronic partial RSD paradigm using the multiple platform technique. The CB1R antagonist rimonabant (1 or 3 mg/kg, i.p.) was administered either at one hour prior to the sample phase for acquisition, or immediately after the sample phase for consolidation, or at one hour before the test phase for retrieval of NOR memory. For the reconsolidation task, rimonabant was administered immediately after the second sample phase. ResultsThe RSD episode impaired acquisition, consolidation, and retrieval, but it did not affect the reconsolidation of NOR memory. Rimonabant administration did not affect acquisition, consolidation, and reconsolidation; however, it attenuated impairment of the retrieval of NOR memory induced by chronic RSD. ConclusionsThese findings, along with our previous report, would seem to suggest that RSD may affect different phases of recognition memory based on its duration. Importantly, it seems that the CB1R may, at least in part, be involved in the adverse effects of chronic RSD on the retrieval, but not in the acquisition, consolidation, and reconsolidation, of NOR memory.