The effect of soluflazine on adenosine receptors in the rat brain

Soluflazine, a potent adenosine transport inhibitor, was intracerebroventricularly administered to rats via ALZET mini osmotic pumps (4nmole, 0.5 L/hr) for 14 days and the effect on adenosine receptors was determined in specific brain areas. Soluflazine decreased adenosine A1 radioligand binding in the hippocampus as measured by [3H]R-PIA, and lowered adenosine A2 binding sites in the striatum, as estimated by the "NECA minus R-PIA" assay. Previous work from our lab has shown the ability of diazepam and triazolam to decrease adenosine binding in the same brain areas. The data show that a specific adenosine transport inhibitor produces the same effect on adenosine receptors as benzodiazepines, and suggest a role for adenosine in the CNS effects of benzodiazepines.     

The effect of clomipramine on wake/sleep and orexinergic expression in rats

We have previously found that neonatal treatment with clomipramine (CLI) induced a decrease in brain orexins during the juvenile period and that these changes were reversed at adulthood. This study investigated the effect of CLI on the orexinergic component and sleep/wake states. Two groups of adult male rats were conducted for 48-h polysomnographic recording. One group of rats was treated with CLI (20 mg/kg every 12 h), and a second group was treated with equivolume of saline (SAL) simultaneously after the first 24 h of polysomnographic recording. Rats were killed 2 h after the third dose of treatment. Brain tissues were collected for radioimmunoassay quantification of orexins and real-time PCR analysis of prepro-orexin and orexin receptor mRNA. The CLI group had significantly shorter rapid eye movement (REM) sleep and longer REM latency compared with both the baseline day and the SAL group and had significantly less active wake and more quiet wake. Compared with the control rats, the CLI rats had significantly higher mRNA expression of prepro-orexin in the hypothalamus and the frontal cortex, but not in the hippocampus. The CLI rats also had significantly less orexin B in the hypothalamus than the control rats. These results suggest that suppression of active wake and orexin B by CLI may be a factor responsible for CLI-induced depression and that the increase of prepro-orexin mRNA may be a sign of increased brain orexins found in this model.     

Lack of effect of 1-methylisoguanosine on sleep in rats

The dose-response effects of intracerebroventricular (i.c.v.) administration of 1-methylisoguanosine (MIG) on sleep in rats were examined. Not even the largest dose (100 nmol/rat) of 1-methylisoguanosine produced significant hypnotic effects, whereas doses of 10 and 100 nmol/rat suppressed rapid eye movement sleep in rats. The only statistically significant effect of 1-methylisoguanosine on sleep latencies was an increase in the latency of S2 after intracerebroventricular administration of 100 nmol/rat of the drug. These effects of 1-methylisoguanosine on sleep were unlike those of both adenosine and the benzodiazepines, suggesting that, contrary to earlier speculations, 1-methylisoguanosine does not interact with central adenosine or benzodiazepine receptors.     

刺五加注射液对大鼠睡眠影响的实验研究

目的 探讨刺五加注射液对SD大鼠睡眠周期的影响.方法 将30只大鼠随机分为2组,刺五加组和对照组,分别连续7 d腹腔注射刺五加注射液和0.9%氯化钠溶液,通过记录大鼠的脑电及肌电活动,了解药物对睡眠周期的影响.结果 与对照组比较,刺五加组大鼠从第5天开始睡眠周期发生较显著的变化.总睡眠时间(TST)显著增加(P<0.05),其中以慢波睡眠(SWS)的增加最为显著(P<0.05),而异相睡眠(PS)的变化组间差异无统计学意义(P>0.05).第9天时作用最明显,深慢波睡眠(SWS2)、SWS和TST分别增加104.3%、27.3%和31.3%(P均<0.01);觉醒期(W)减少38.9%(P<0.01).注射后第13天睡眠开始恢复正常.结论 刺五加注射液能选择性增加睡眠周期中的SWS,在治疗睡眠障碍方面具有较大的优越性.     

Short-term REM sleep deprivation effect on temperature rhythm of rats

Circadian rhythm of body temperature (CRT) is altered in endogenous depression and many psychiatric disorders. Even the sleep pattern is disrupted. Sleep deprivation alleviates symptoms in depression. The present study was conducted to find the role of noradrenergic innervation to the pineal gland in bringing about the effect of REM sleep deprivation (REMSD) on the CRT. Adult male Wistar rats (n = 12) divided into 2 groups were used for the study. The group I rats (n = 6) underwent superior cervical ganglionectomy and the group II rats (n = 6) were sham ganglionectomised. After recovery rats were given REMSD for 48 hours. The CRT was measured in three periods of the study i.e. basal, post operative and post REMSD. The results indicated REMSD increased the Amplitude and Mesor of the CRT in both the groups which was shortlasting and reversible thus suggesting non sympathetic mediation of the pineal in bringing about the circadian rhythm alteration due to REMSD.     

The effect of melatonin on normal sleep

We examined the effect of 1-mg and 5-mg oral dosages of melatonin on the electroencephalogram-recorded sleep of ten normal subjects in a randomized, double-blind design. Although high dosages of melatonin have previously been reported to be a sedative and to have behavioral effects, we could not find any change in onset or duration of sleep, or any effect on mood or alertness the following day using these low dosages. An increase in rapid eye movement (REM) latency was noted at the 5-mg dose, but no other parameter of REM sleep was changed.     

脑脊液5-羟色胺浓度对大鼠中枢性睡眠呼吸暂停的影响

目的探讨脑脊液5-羟色胺(5-HT)浓度对中枢性睡眠呼吸暂停的影响。方法对8只成年雄性SD大鼠进行连续3d的睡眠呼吸监测,第1天为空白(A组),第2天给予新鲜脑脊液(ACSF)(B组),第3天给予5-HT(C组)。记录呼吸暂停指数、睡眠效率、各期睡眠时间,进行重复测量资料的方差分析。结果 (1)C组非快速眼动期呼吸暂停指数较A组和B组明显降低(P<0.05)。(2)C组快速眼动期(REM期)叹息后呼吸暂停指数较A组明显降低(P=0.019)。(3)三组在REM期自发性呼吸暂停指数、睡眠效率、NREM期睡眠时间上差异无统计学意义。(4)C组REM期睡眠时间较A组明显减少(P=0.038)。结论提高脑脊液5-HT浓度可改善SD大鼠NREM期睡眠呼吸暂停及REM期叹气后呼吸暂停,对SD大鼠睡眠效率及NREM期睡眠时间无影响。     

The effect of δ 9-tetrahydrocannabinol on sleep

Five volunteers slept 8 to 15 consecutive nights in the laboratory with electroencephalogram, chin electromyogram, and eye movements monitored by the method originated by Dement and Kleitman. ⁹-tetrahydrocannabinol (THC), 20 mg administered at bedtime decreased the amount of time spent in the REM or paradoxical phase of sleep. Abrupt withdrawal of THC after 4 to 6 consecutive nights of use produced a mild insomnia characterized by difficulty in falling and staying asleep but did not produce a marked REM rebound.     

The effect of ofloxacin on pentobarbital-induced sleep in mice.

There have been several reports that insomnia occurs in some patients who receive ofloxacin. Since almost no experimental data on ofloxacin-induced insomnia were available, this study was conducted for the evaluation of ofloxacin effects on sleep parameters in mice. In Experiment 1, mice were pretreated with ofloxacin (20 or 40 mg/kg IP) or saline 15 minutes before sodium pentobarbital (35 mg/kg IP). Experiment 2 was carried out in two days. On the first day mice were treated twice, in the morning and in the evening, with ofloxacin (20 or 80 mg/kg IP) or saline. On the second morning, mice were pretreated with the same doses of ofloxacin or saline 15 minutes before sodium pentobarbital (35 mg/kg IP). Sleep latency and sleeping time were recorded in each experiment. Results showed that ofloxacin had no apparent effect on sleep latency, but caused a shortening in sleeping time. However, this effect was significant only in the 40 and 80 mg/kg ofloxacin-treated groups.     

The effect of escitalopram on sleep problems in depressed patients

The results from three 8-week escitalopram studies in major depressive disorder are presented with respect to efficacy and the effect on sleep quality, both in the full population and the subpopulation of patients with sleep problems at baseline.Analysis of pooled data from these randomized, double-blind, placebo-controlled, studies in which citalopram was the active reference, showed a significant improvement for escitalopram-treated patients (n = 52.0) in the Montgomery-Asberg depression rating scale (MADRS) item 4 ('reduced sleep') scores at weeks 6 and 8 compared with placebo (n=398; p < 0.01) and at weeks 4, 6 and 8 (n = 403; p < 0.05) compared with citalopram.Escitalopram-treated patients with sleep problems (MADRS item 4 score > or = 4; n = 254) at baseline showed a statistically significant improvement in mean MADRS item 4 scores at weeks 4, 6 and 8 compared with patients treated with placebo (n = 191; p < 0.05) or citalopram (n = 193; p < 0.01). These patients also showed a statistically significant (p < 0.05) and clinically relevant improvement in MADRS total score after escitalopram treatment compared with citalopram at weeks 1, 4, 6 and 8 (observed cases) and endpoint (-2.45; last observation carried forward [LOCF]). Statistical significance in favour of escitalopram versus placebo treatment was found at all visits, including endpoint (-4.2; LOCF).Thus, these post-hoc analyses suggest that escitalopram has a significant beneficial effect compared with placebo or citalopram in reducing sleep disturbance in patients suffering from major depressive disorder. The effect of escitalopram in improving 'reduced sleep' scores was clearly seen in patients with more severe sleep disturbance at baseline. A further prospective study is needed to establish this useful clinical effect in insomniac depressives.     

The effect of triazolam on the sleep of insomniacs

The effects of three oral doses of bedtime triazolam (0.25 mg, 0.5 mg, and 1.0 mg) a new benzodiazepine, on the laboratory sleep of insomniacs were studied in a double blind design which used the following 14 consecutive night schedule: 1–4 placebo; 5–11 drug; 12–14 placebo. Effects on sleep were measured objectively by conventional EEG/EOG/EMG sleep recordings and subjectively by questionnaires administered each morning. Side or toxic effects were assessed by screening physicals and questionnaires administered each morning and each evening and by a comparison of the prestudy vs. end-study physical exams and clinical lab tests. At the 0.5 mg dose triazolam significantly reduced several objective and subjective measures of insomnia. It had lesser effects at the 0.25 mg dose and equal or greater effects at 1.0 mg dose. There were no remarkable side or toxic effects at any dose.     

The effect of methyl phenidate on the sleep cycle in man

Summary The EEGs and electrooculograms of 6 Ss were recorded for six hours on four nights in the laboratory. On two nights the Ss received methyl phenidate at a 5-mg dose level, and on two other nights they received a placebo. The drug significantly delayed the onset of the first REM period. It also significantly reduced the amount of REM sleep and increased the time spent in stage-2 sleep during the six-hour period of observation. It exerted these effects without significantly affecting any of the other parameters of the sleep cycle that were studied.This study was conducted in the Psychology Laboratory and the Psychiatric Treatment Research Center of the Department of Psychiatry, and was supported by grants from the National Institutes of Health, United States Public Health Service, nos. 5-K3-MH-23,901 and 5-RO1-MH10088.I would like to thank Dr. Arthur Shapiro for his advice in the preparation of this paper.     

Influence of thiopental on sleep cycles in rats

Summary Thiopental, in doses of 20–40 mg/kg s. c. in 1 ml of infusion fluid injected during 75 min, was administered to sleeping rats with electrodes implanted in the cortex and hippocampus. The drug-effect on the sleep cycles has been investigated.Increasing doses of thiopental (from 40–60 mg/kg total doses s.c. upwards) induce a gradual prolongation of the duration of the slow wave sleep phase. The length of the paradoxical sleep phase does not change but suddenly disappears completely into a sleep-anaesthesia which is characterized by continuous irregular slow wave activity.After 30 mg/kg (total dose s.c.) the spindle type cortical activity, characteristically appearing the beginning of paradoxical phase, becomes more prominent, lasts longer and with increasing doses gradually spreads over the whole paradoxical phase. At the same time the frequency of theta activity during the paradoxical phase decreases gradually from 7–5 per sec.A preliminary report was given at the Annual Meeting of the Czechoslovak Society for Higher Nervous Activity in October 1965 (Stýblová, V., and T. Radil-Weiss, 1966).     

Influence of atropine on sleep cycle in rats

Summary In freely moving rats with implanted electrodes the influence of subcutaneously administered atropine sulphate on EEG signs of sleep cycles was analysed. Four subsequent single doses of 0.75; 1.0; 1.25; 2.25 or 3.0 mg/kg of atropine repeated in 30 min intervals were applied, the total doses being 3.0; 4.0; 5.0; 9.0 resp. 12 mg/kg.Even after high doses of atropine sulphate about 40% of the sleep EEG activity is covered by sleep cycles (regular alternation of generalized slow wave activity with neocortical desynchronization combined with hippocampal theta activity) not differing from normal cycles significantly, the rest being a generalized high voltage slow wave irregular activity.After atropine hippocampal theta activity during phase 2 shows, in contradistinction to control records, a spontaneous recruiting like, spindle-like alternation of the amplitude of the waves interrupted by periods of irregular activity.After atropine the arousing effects of reticular stimulation (repeated regularly in 1 min intervals) becomes less pronounced, the incidence of arousal reactions after uniform stimuli being significantly decreased. Nevertheless, the gradual decrease of reticular excitability during the last part of phase 1 of sleep can still be demonstrated.On leave from Instituto de Estudios Médicos y Biológicos, UNAM México     

牛磺酸对大鼠高血压的影响

在大鼠腹主动脉狭窄和高盐摄入引起的高血压模型上,观察到口服牛磺酸治疗可显著降低动物血压,(20.8±4.0kPa VS非治疗组27.3±3.2 kPa.P<0.01)抑制高血压动物血浆CGRP的减少.改善动物血管条的舒张反应。实验结果提示,牛磺酸可能具有临床上抗高血压作用。     

The phosphorylated analogue of DSIP enhances slow wave sleep and paradoxical sleep in unrestrained rats

Continued 10-h nocturnal intracerebroventricular infusion of 0.5 nmol P-DSIP, the phosphorylated analogue of delta-sleep-inducing peptide (DSIP), significantly increased slow wave sleep (22%) and paradoxical sleep (81%) in unrestrained rats. The increase in the amount of sleep was largely due to an increase in the number of sleep episodes. Larger and smaller doses were ineffective in doses ranging from 0.025 to 25 nmol. The sleep-promoting potency of P-DSIP was 5 times greater than that of DSIP compared by the same assay.     

阻塞性睡眠呼吸暂停综合征对代谢综合征的影响

目的探讨阻塞性睡眠呼吸暂停综合征(OSAS)对血压、糖、脂代谢及胰岛素敏感性的影响,以及持续正压通气(CPAP)对其疗效.方法36例OSAS患者与12例正常者分别比较呼吸暂停通气指数(AHI)、经皮血氧饱和度(SpO2)、空腹血糖、血脂、血胰岛素水平以及胰岛素敏感指数(ISI)、血压、体重指数等指标.OSAS组经CPAP治疗后复查上述指标并进行统计学分析.结果CPAP组与正常组相比,前者AHI(38.7±6.5次/h)、空腹血糖(5.8±0.5mmol/L)、胆固醇(5.8±0.4mmol/L)、甘油三脂(1.9±0.3mmol/L)、低密度脂蛋白胆固醇(LDLc)(3.2±0.3mmol/L)、空腹血胰岛素水平(19.8±2.4mU/L)、收缩压(143.1±11.7)、舒张压(87.8±8.6)、体重指数(28.2±2.1kg/m2)较后者明显增高,SpO2(89.6±3.1%)、高密度脂蛋白胆固醇(HDLc)(1.2±0.3mmol/L)、ISI(-2.06±0.07)较后者明显减低,p均＜0.01.治疗后,CPAP除组体重指数(27.1±1.9kg/m2)外,AHI(26.9±5.2次/h)、空腹血糖(5.2±0.4mmol/L)、胆固醇(5.3±0.3mmol/L)、甘油三脂(1.6±0.2mmol/L)、LDLc(2.8±0.3mmol/L)、血胰岛素水平(16.1±1.9mU/L)、收缩压(137.1±8.8)、舒张压(81.9±7.8)较治疗前明显降低,p均＜0.05;SpO2(92.8±2.0%)、HDLc(1.4±0.3mmol/L)、ISI(-1.92±0.08)明显增高,p＜0.05.结论OSAS患者存在血压、糖、脂代谢异常以及胰岛素抵抗可能,CPAP治疗能改善OSAS患者的代谢综合征.     

The involvement of PTEN in sleep deprivation-induced memory impairment in rats

Although the underlying mechanism is not elucidated, it has been postulated repeatedly that deprivation of sleep, particularly rapid eye movement (REM) sleep, affects learning. Here we report that memory for newly acquired information is impaired after a specific period of REM sleep deprivation (REMD). Memory retrieval-induced phosphorylation of protein kinases in the rat amygdala is abrogated by REMD that is associated with an increase in the expression of a dual protein/lipid phosphatase PTEN. REMD given before training is without effect, suggesting the lack of effect on the acquisition of memory. Intra-amygdala administration of antisense but not sense or scrambled oligonucleotides for PTEN prevents REMD-induced decrease in protein phosphorylation and impairment of fear memory. Thus, REMD interferes with the process of memory retention via the activation of PTEN.     

Caffeine during sleep deprivation: sleep tendency and dynamics of recovery sleep in rats

The adenosine antagonist caffeine disrupts sleep, but whether caffeine promotes wakefulness by interfering with the expression of sleep or by attenuating sleepiness is unknown. The ability of caffeine to reduce sleep tendency in rats was directly tested by quantifying the number of stimuli needed to maintain wakefulness during sleep deprivation for 6 h after systemic caffeine treatment. In addition, the influence of caffeine on the dynamics between nonrapid-eye-movement (NREM) and rapid-eye-movement (REM) sleep was investigated by comparing the magnitude and time course of the compensatory sleep responses for 42 h postsleep deprivation. Caffeine significantly reduced the attempts to sleep during sleep deprivation, F(1,9) 8.83, p = 0.0157; 44.9% of vehicle), but did not change compensatory slow-wave activity during recovery sleep. During the initial recovery phase, caffeine suppressed compensatory REM sleep and reduced, but did not block, compensatory NREM sleep duration and continuity. By 42 h postsleep deprivation, the amount of NREM recovered (70.0% of deficit) did not differ from vehicle. In contrast, the REM sleep deficit recovered after caffeine (100%) was more than after vehicle (43.9%). Thus, caffeine slowed the rate of compensatory sleep after sleep deprivation, as indexed by the duration of sleep states and sleep continuity.