Mu-delta opioid interactions. II: Beta-FNA inhibits DPDPE-induced increases in morphine EEG and EEG spectral power.

In the present study, the effects of beta-FNA on DPDPE-induced increases in morphine EEG and EEG power spectra were assessed. Adult female Sprague-Dawley rats were implanted with cortical EEG electrodes and permanent indwelling ICV and IV cannulae. Rats were administered ICV beta-FNA at 20 nmol or ICV sterile water. Then 18-24 h later, rats were administered ICV DPDPE at 2.5 nmol or ICV sterile water followed, 10 min later, by IV morphine at 3 mg/kg. Morphine-induced changes in EEG global (1-50 Hz) spectral parameters, the duration of morphine-induced high voltage EEG bursts, the period of EEG and behavioral excitation, and the latency to onset of slow-wave sleep were statistically analyzed using a one-way analysis of variance. beta-FNA pretreatment significantly decreased morphine-induced total spectral power seen in the DPDPE + morphine group. beta-FNA pretreatment also significantly decreased the duration of morphine-induced EEG bursts, the period of EEG and behavioral excitation, and the latency to onset of slow-wave sleep in the DPDPE + morphine group. These data, therefore, suggest that DPDPE may be increasing the effects of morphine on EEG through delta opioid receptors associated with the mu-delta opioid receptor complex.     

Sleep and EEG spectra in the Syrian hamster (Mesocricetus auratus) under baseline conditions and following sleep deprivation

Summary Sleep was studied by continuous 24-h recordings in adult male Syrian hamsters, chronically implanted with EEG and EMG electrodes. Three vigilance states were determined using visual scoring and EEG power spectra (0.25–25 Hz) computed for 4-s episodes.The effects of two methods of total sleep deprivation (SD) were examined on vigilance states and the EEG power spectrum. The animals were subjected to 24 h SD by: (1) forced locomotion in a slowly rotating drum, (2) gentle handling whenever the hamsters attempted a sleeping posture. In addition, the hamsters were subjected to SD by handling during the first 3 h of the L period.Sleep predominated in the L period (78.2% of 12 h) and the D period (51.2%). The power spectra of the 3 vigilance states were similar during the L and D period. In NREM sleep, power density values in the low frequency range (0.25–6.0 Hz) exceeded those of REM sleep and W by a maximum factor of 8.3 and 2.8, respectively. At frequencies above 16 Hz, NREM and REM sleep power density values were significantly lower than during W. A progressive decrease in power density for low EEG frequencies (0.25–7 Hz) during NREM sleep was seen in the course of the L period. Power density values of higher frequencies (8–25 Hz) increased at the end of the L period and remained high during the first hours of the D period.The effect of prolonged SD on vigilance states and EEG spectra was similar by both methods and strikingly small compared to similar results in rats. In contrast, 3 h SD induced a large and more prolonged effect. The similarities and differences of sleep and sleep regulation are summarized for the hamster, rat and man.Abbreviations EEG electroencephalogram - LD light dark - REM rapid eye movements - NREM sleep non REM sleep - W waking - SD sleep deprivation - TST total sleep time - L light - D dark     

Docosahexaenoic acid, but not eicosapentaenoic acid, reduces the early inflammatory response following compression spinal cord injury in the rat

Docosahexaenoic acid (DHA, 22 : 6) and eicosapentaenoic acid (EPA, 20 : 5) are omega-3 polyunsaturated fatty acids (n-3 PUFAs) with distinct anti-inflammatory properties. Both have neuroprotective effects acutely following spinal cord injury (SCI). We examined the effect of intravenous DHA and EPA on early inflammatory events after SCI. Saline, DHA or EPA (both 250 nmol/kg) were administered 30 min after T12 compression SCI, to female Sprague-Dawley rats. DHA significantly reduced the number of neutrophils to some areas of the injured epicentre at 4 h and 24 h. DHA also reduced C-reactive protein plasma levels, whereas EPA did not significantly reduce neutrophils or C-reactive protein. Laminectomy and SCI elicited a sustained inflammatory response in the liver, which was not reversed by the PUFAs. The chemokine KC/GRO/CINC and the cytokine IL-6 provide gradients for chemotaxis of neutrophils to the epicentre. At 4 h after injury, there was a significant increase in IL-6, KC/GRO/CINC, IL-1β and tumour necrosis factor-α in the epicentre, with a return to baseline at 24 h. Neither DHA nor EPA returned their levels to control values. These results indicate that the acute neuroprotective effects of n-3 PUFAs in rat compression SCI may be only partly attributed to reduction of some of the early inflammatory events occurring after injury.     

遗传性大鼠脐疝模型的选育

目的近交繁殖先天性脐疝大鼠获得能稳定遗传的大鼠脐疝模型,大鼠脐疝结构观察及治疗。方法每代大鼠全同胞交配,记录产子数及脐疝情况,分析大鼠脐疝率;取F2代6月龄脐疝雌雄大鼠各6只,其中雌雄各2只进行解剖观察,雌雄大鼠各4只进行外科手术缝合。结果随近交系数增大,大鼠脐疝率升高,F12、F13代大鼠均为脐疝;F1代至F13代雌性大鼠总体脐疝率显著高于雄性大鼠（x2=11.1,P=0.001）;雌雄大鼠脐疝结构一致,手术后3~4周痊愈无复发。结论经连续13代全同胞交配获得了遗传性状稳定的大鼠脐疝模型。     

Cardiopulmonary regulation after rapid-eye-movement sleep deprivation.

Arterial blood pressure, chest movement, electroencephalogram, and electromyogram were monitored in six normotensive Sprague-Dawley rats for 4 h/day 3 days before and 4 days after 114 h of rapid-eye-movement (REM) sleep deprivation. During recovery sleep immediately after REM sleep deprivation (RD), there was a significant increase in the amount of time spent in REM sleep. During this rebound in REM sleep, there was a significant rise (26%) in heart rate in wakefulness, non-REM sleep, and REM sleep during the first 4 h after RD. Systolic blood pressure was also significantly elevated (14%) but only during wakefulness before recovery sleep. Rats with the greatest waking systolic blood pressure after RD had the lowest REM sleep rebound in the 4 h immediately after RD (r = -0.885, P less than 0.05). The rise in heart rate, systolic blood pressure, and REM sleep time evident on day 1 immediately after RD was absent on recovery days 2-4. The respiratory rate tended to be higher throughout the recovery period in every state of consciousness; however, these values never reached the level of significance. In the initial recovery sleep period, regulation of heart rate was more disrupted by REM sleep deprivation than either arterial blood pressure or respiratory rate.     

Electrical activity of the neocortex in adult rats after prenatal hypoxia and in epilepsy model

Changes in electrical activity of the neocortex after prenatal hypoxia (day 14 of embryogenesis, E14, 7% O₂ for 3 h) and intracortical microinjection of epileptogenic 4-aminopyridine (4-AP) were studied in adult (3-month-old) rats. The frequency–time parameters of electrocorticogram (ECoG) were analyzed during sleep and wakefulness as well as in a model of 4-AP-induced spike-wave discharge (SWD) epileptiform activity. The results showed that in rats exposed to prenatal hypoxia the theta rhythm had a lower frequency while sleep spindles displayed a lower spectral power in the low-frequency range as compared to the control group. In rats with prenatal pathology, there was revealed a delayed onset of epileptiform activity and a shifted frequency distribution of the SWD spectral power induced by 4-AP.     

Reactive oxygen species contribute to sleep apnea-induced hypertension in rats

In clinical studies, sleep apnea is associated with hypertension, oxidative stress, and increased circulating endothelin-1 (ET-1). We previously developed a model of sleep apnea by exposing rats to eucapnic intermittent hypoxia (IH-C) during sleep, which increases both blood pressure and plasma levels of ET-1. Because similar protocols in mice increase tissue and plasma markers of oxidative stress, we hypothesized that IH-C generation of reactive oxygen species (ROS) contributes to the development of ET-1-dependent hypertension in IH-C rats. To test this, male Sprague-Dawley rats were instrumented with indwelling blood pressure telemeters and drank either plain water or water containing the superoxide dismutase mimetic, Tempol (4-hydroxy-2,2,6,6-tetramethyl-piperidine-1-oxyl, 1 mM). Mean arterial pressure (MAP) and heart rate (HR) were recorded for 3 control days and 14 treatment days with rats exposed 7 h/day to IH-C or air/air cycling (Sham). On day 14, MAP in IH-C rats treated with Tempol (107 +/- 2.29 mmHg) was significantly lower than in untreated IH-C rats (118 +/- 9 mmHg, P < 0.05). Tempol did not affect blood pressure in sham-operated rats (Tempol = 101 +/- 3, water = 101 +/- 2 mmHg). Immunoreactive ET-1 was greater in plasma from IH-C rats compared with plasma from sham-operated rats but was not different from Sham in Tempol-treated IH-C rats. Small mesenteric arteries from IH-C rats but not Tempol-treated IH-C rats had increased superoxide levels as measured by ferric cytochrome c reduction, lucigenin signaling, and dihydroethidium fluorescence. The data show that IH-C increases ET-1 production and vascular ROS levels and that scavenging superoxide prevents both. Thus oxidative stress appears to contribute to increases in ET-1 production and elevated arterial pressure in this rat model of sleep apnea-induced hypertension.     

Time-of-day modulation of homeostatic and allostatic sleep responses to chronic sleep restriction in rats

To study sleep responses to chronic sleep restriction (CSR) and time-of-day influences on these responses, we developed a rat model of CSR that takes into account the polyphasic sleep patterns in rats. Adult male rats underwent cycles of 3 h of sleep deprivation (SD) and 1 h of sleep opportunity (SO) continuously for 4 days, beginning at the onset of the 12-h light phase ("3/1" protocol). Electroencephalogram (EEG) and electromyogram (EMG) recordings were made before, during, and after CSR. During CSR, total sleep time was reduced by ～60% from baseline levels. Both rapid eye movement sleep (REMS) and non-rapid eye movement sleep (NREMS) during SO periods increased initially relative to baseline and remained elevated for the rest of the CSR period. In contrast, NREMS EEG delta power (a measure of sleep intensity) increased initially, but then declined gradually, in parallel with increases in high-frequency power in the NREMS EEG. The amplitude of daily rhythms in NREMS and REMS amounts was maintained during SO periods, whereas that of NREMS delta power was reduced. Compensatory responses during the 2-day post-CSR recovery period were either modest or negative and gated by time of day. NREMS, REMS, and EEG delta power lost during CSR were not recovered by the end of the second recovery day. Thus the "3/1" CSR protocol triggered both homeostatic responses (increased sleep amounts and intensity during SOs) and allostatic responses (gradual decline in sleep intensity during SOs and muted or negative post-CSR sleep recovery), and both responses were modulated by time of day.     

Effects of paradoxical sleep deprivation on genital reflexes in five rat strains

This study examined the effects of cocaine on genital reflexes in paradoxical sleep-deprived (PSD) male rats of five strains since it has been demonstrated that this drug enhances genital reflexes in Wistar PSD rats. At the end of a 4-day period of PSD or at the equivalent time-point to control animals, cocaine or saline was acutely administered to the animals and penile erection (PE) and ejaculation (EJ) were quantified. Results indicated that PSD induced genital reflexes in all strains, and cocaine potentiated these behaviors in Wistar and Long-Evans rats. Wistar PSD rats injected with cocaine performed significantly more PE than all the other PSD + cocaine strains. The number of Wistar and Long-Evans PSD + cocaine ejaculating was significantly higher than the respective PSD + saline and control, whereas a tendency of increase was seen in relation to other groups. Wistar PSD + cocaine rats showed the highest EJ frequency compared to F344, Sprague-Dawley and Wistar-Kyoto strains, and the Long-Evans displayed more EJ than Sprague-Dawley and Wistar-Kyoto. Analysis of testosterone concentrations revealed that after sleep deprivation, Wistar, Long-Evans, and F344 rats showed significantly lower testosterone concentrations than control rats. In F344, Sprague-Dawley and Wistar-Kyoto controls rats, testosterone was significantly lower than in the control Wistar and Long-Evans. Progesterone concentrations were significantly higher in Wistar and Long-Evans PSD rats than in respective control groups. In the other strains, this hormone was significantly lower compared to the Wistar and Long-Evans PSD. This study demonstrates that genital reflexes are differently influenced by PSD associated to cocaine in five rat strains.     

Spontaneous K-Complex Density in Slow-Wave Sleep

Purpose

To study spontaneous K-complex (KC) densities during slow-wave sleep. The secondary objective was to estimate intra-non-rapid eye movement (NREM) sleep differences in KC density.

Materials and Methods

It is a retrospective study using EEG data included in polysomnographic records from the archive at the sleep research laboratory of the Centre for Physiotherapy and Rehabilitation Sciences, Jamia Millia Islamia, India. The EEG records of 4459 minutes were used. The study presents a manual identification investigation of KCs in 17 healthy young adult male volunteers (age = 23.82±3.40 years and BMI = 23.42±4.18 kg/m²).

Results

N3 had a higher KC density than N2 (Z = -2.485, p = 0.013) for all of the probes taken together. Four EEG probes had a higher probe-specific KC density during N3. The inter-probe KC density differed significantly during N2 (χ² = 67.91, p < .001), N3 (χ² = 70.62, p < .001) and NREM (χ² = 68.50, p < .001). The percent distribution of KC decreased uniformly with sleep cycles.

Conclusion

The inter-probe differences during N3 establish the fronto-central dominance of the KC density regardless of sleep stage. This finding supports one local theory of KC generation. The significantly higher KC density during N3 may imply that the neuro-anatomical origin of slow-wave activity and KC is the same. This temporal alignment with slow-wave activity supports the sleep-promoting function of the KC.     

Relationship of ethanol blood level to REM and non-REM sleep time and distribution in the rat.

Direct electroencephalographic (EEG) and integrated electromyographic (EMG) recordings were analyzed for possible changes in the REM and non-REM sleep time in chronically implanted rats given 0, 1, 2, and 4 g/kg ethanol. REM and non-REM sleep were found, respectively, to be lessened and elevated in a dose-related manner. The degree of disruption of normal sleep-awake patterns was also found to correspond with blood-ethanol concentrations for the different doses of ethanol. These findings are discussed in relation to the influence of ethanol on the sleep of the human subject and the suggestion that the rat with chronic EEG and EMG electrodes may serve as a model for studying the degree of disruption of sleep upon chronic exposure to ethanol.     

Tocotrienol Levels in Various Tissues of Sprague-Dawley Rats after Intragastric Administration of Tocotrienols

A tocotrienol (T3) mixture was intragastricaly administered to Sprague-Dawley rats, and the T3 levels in various tissues were measured 0, 4, 8 and 24 hr after the administration. In blood clots, brain, thymus, testes, vice-testes and muscles, T3 homologues were not detected at all. In epididymal adipose, renal adipose, subcutaneous adipose and brown adipose tissues and in the heart, the T3 levels were maintained or increased for 24 hr after the administration. In the serum, liver, mesenteric lymph node, spleen and lungs, the T3 levels were highest 8 hr after the T3 administration. These results suggest that the distribution and metabolism of T3 in the rat vary considerably among different tissues.     

Dynamics of spectral characteristics of theta- and alpha-range EEG during negative emotional reactions]

Power characteristics of the EEG theta and alpha rhythms were studied in a human in neutral state and during a conditioned negative emotional reaction (Fp1, Fp2, F3, F4, C3, C4, P3, P4, O1, O2, F7, F8, T3, T4, T5, and T6 derivations). A significant increase in the relative spectral power in the narrow theta band of 7.4-8.1 Hz in the frontocentral and temporal brain regions was observed during the development of the negative emotional reaction. The alpha-rhythm dynamics during the negative reaction was substantially individual and could be expressed in either an increase, or decrease in relative spectral power of different alpha-frequencies. No pronounced changes in their dynamics could also be observed. In some subjects the spectral power of the medium-frequency alpha-rhythm significantly decreased, that of the high-frequency rhythm increased, and changes in the spectral power of the low-frequency alpha range varied.     

Tocotrienol levels in various tissues of Sprague-Dawley rats after intragastric administration of tocotrienols

A tocotrienol (T3) mixture was intragastricaly administered to Sprague-Dawley rats, and the T3 levels in various tissues were measured 0, 4, 8 and 24 hr after the administration. In blood clots, brain, thymus, testes, vice-testes and muscles, T3 homologues were not detected at all. In epididymal adipose, renal adipose, subcutaneous adipose and brown adipose tissues and in the heart, the T3 levels were maintained or increased for 24 hr after the administration. In the serum, liver, mesenteric lymph node, spleen and lungs, the T3 levels were highest 8 hr after the T3 administration. These results suggest that the distribution and metabolism of T3 in the rat vary considerably among different tissues.     

Hepatic triiodothyronine sulfation and its regulation by growth hormone and triiodothyronine in rats.

The regulatory mechanism of cytosolic sulfation of T3 has been studied in rat liver. Sulfation of T3 is sexually differentiated in adult rats of Sprague-Dawley (SD), Fisher 344, and ACI strains. In SD strain, the male animals showed 4 times higher sulfating activity than did the females. The specific activity was decreased by hypophysectomy of male adult rats, but was not affected in the females. Thus, the sex-difference was abolished in the hypophysectomized condition. Supplement of human GH intermittently twice daily for 7 days, to mimic the male secretory pattern, increased T3 sulfating activity in both sexes of hypophysectomized rats, whereas continuous infusion to mimic a female secretory pattern had no appreciable effect. Cytosolic sulfation of T3 was decreased by 25 to 30% by thyroidectomy or propylthiouracil treatment of male adult rats, and was restored by the supplementation of T3 (50 micrograms/kg daily for 7 days) to thyroidectomized rats. Administration of T3 in hypophysectomized rats almost completely restored the sulfating activity in the males and increased the activity in the females. Cytosolic T3 sulfation was inhibited by the addition of known inhibitors of phenol sulfotransferase, pentachlorophenol or 2,6-dichloro-4-nitrophenol. These results indicate a role of pituitary GH in hepatic sulfation of thyroid hormones in rats. The data obtained also raise the possibility that GH may modify the effect of thyroid hormones on the pituitary by a feed-back mechanism through changing the level of a sex-dominant phenol sulfotransferase(s) in rat livers. T3 was also sulfated in hepatic cytosols of mouse, hamster, rabbit, dog, monkey, and human.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sleep EEG spectral analysis in a diurnal rodent:Eutamias sibiricus

1. Sleep was studied in the diurnal rodent Eutamias sibiricus, chronically implanted with EEG and EMG electrodes. Analysis of the distribution of wakefulness, nonrapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep over the 24 h period (LD 12:12) showed that total sleep time was 27.5% of recording time during the 12 h light period and 74.4% during the 12 h dark period. Spectral analysis of the sleep EEG revealed a progressive decay in delta power density in NREM sleep during darkness. Power density of the higher frequencies increased at the end of darkness. Power density of the higher frequencies decreased and that of the lower frequencies increased during light. 2. Analysis of the distribution of vigilance states under three different photoperiods (LD 18:6; 12:12; 6:18) revealed that changes in daylength mainly resulted in a redistribution of sleep and wakefulness over light and darkness. Under long days the percentage of sleep during light was enhanced. The time course of delta power density in NREM sleep was characterized by a long rising part and a short falling part under long days, while a reversed picture emerged under short days. As a consequence, the power density during days. As a consequence, the power density during light was relatively high under long days. 3. After 24 h sleep deprivation by forced activity, no significant changes in the percentages of wakefulness and NREM were observed, whereas REM sleep was slightly enhanced. EEG power density, however, was significantly increased by ca. 50% in the 1.25-10.0 Hz range in the first 3 h of recovery sleep. This increase gradually decayed over the recovery night. 4. The same 24 h sleep deprivation technique led to a ca. 25% increase in oxygen consumption during recovery nights. While the results of the EEG spectral analysis are compatible with the hypothesis that delta power density reflects the 'intensity' of NREM sleep as enhanced by prior wakefulness and reduced by prior sleep, such enhanced sleep depth after sleep deprivation is not associated with reduced energy expenditure as might be anticipated by some energy conservation hypotheses on sleep function.     

Direct up-regulation of estrogen receptor by triiodothyronine in rat pituitary tumor MtT/F84.

To investigate a possible effect of triiodothyronine (T3) on the regulation of estrogen receptor, estrogen dependent rat pituitary tumor, MtT/F84, was studied in rats which received surgical thyroidectomy (Tx) or were given propylthiouracil (PTU) and were supplemented with T3. In T3 loaded rats, the grafted tumor showed high estrogen receptor levels (160-200% of control), whereas low estrogen receptor levels (20-35% of control) were observed in the tumors grown in Tx and PTU treated rats. A single injection of T3 to Tx rats with MtT/F84 increased the estrogen receptor level in a time dependent manner and reached the maximal level at 6 h. In primary culture of MtT/F84 cells, T3 increased the specific 3H-estrogen binding to tumor cells in a dose dependent manner (165% of control by 10(-7)M T3) and also in a time dependent (maximum at 12 h) manner. These data suggest that T3 directly up-regulates the estrogen receptor level in MtT/F84 cells.     

Groups of passive and active control state in longitudinal experiments: an electrophysiological study

Long-term electrophysiological experiments were carried out with rats with chronically implanted electrodes into dopaminergic brain structures. Within 4 weeks after surgery, the relative spectral power of electrical activity in the delta1 and delta2 frequency bands decreased, while the relative spectral power in the alpha, beta1 and beta2 bands increased. A delayed (to the 4-5th week after surgery) increase in the total amount of sleep and REM sleep percent was observed in the sleep architecture of these animals. Multiple (during 2 weeks daily) intraperitoneal saline injections altered the dynamic of electrophysiological indices on the 2nd-3rd postsurgery weeks. The total sleep amount being not increased, the total and mean REM sleep durations increased, and the dynamic of the relative spectral power of electrical activity in the dopaminergic brain structures in the delta1, alpha and beta2 bands was found to be changed.     

组织学与核磁共振检测大鼠癫痫源性早期脑损伤的跨半球扩布特征

侵性强直电刺激(60Hz,2s)大鼠右侧背海马(hippocampus,DHPC)CAl基树突区,1次/d,连续刺激10d。分别在施加强直电刺激的第2、4、6、8或10d时进行核磁共振成像检测(T2 weighted magnetic resonamce image T2-WI),并对鼠脑进行组织学切片鉴定。结果表明,早期慢性癫痫源性脑损伤的病理性形态特征主要包括：(1)T2-WI检测侧脑室(lateral ventricle,LV)区域信号增强、组织学检测LV扩大和双侧对称性脉络膜丛病理性增生,后两者并非完全平行呈现。(2)组织学切片显示双侧LV扩大面积与T2-WI信号增强区域面积的脑区分布近似。与空白对照组大鼠相比,电刺激2、4、6、8和10d后,T2-WI信号增强区域面积显著增大(P=0．0259;P＝0．0184;P=0．0184;P＝0．0404;P＝0．0259)以及组织学鉴定LV面积增大(P＝0．0210;P＝0．01;P＝0．0100;P=0．0152).(3)定侧分析显示,T2-WI信号增强以及T2-WI信号增强区域面积和组织学鉴定LV面积扩大,在慢性刺激6d时均以植入电极的对侧为主;第10d时均以同侧为主。三项观察结果的一致性证实了癫痫源性早期脑损伤的跨半球动态扩布特征。     

State and chemical drive modulate respiratory variability.

The quantification of respiratory variability may provide insight into the integrative control of breathing. To test the hypothesis that sleep and/or increased chemical drive modifies respiratory variability, six male adult Sprague-Dawley rats were instrumented with diaphragm electromyographic (EMG) electrodes and exposed to 0, 2.5, and 5.0% CO2 with a balance of room air during wakefulness and behaviorally determined sleep. Respiratory interval (Ttot), peak diaphragm EMG, and ventilation index (peak diaphragm EMG/Ttot) were calculated for 1,024 sequential breaths. The variability of breathing was quantified with a measurement of signal complexity, the approximate entropy, and two autocorrelation measurements, the autoregressive power spectrum slope and the detrended fluctuation analysis slope. Elevated chemical drive and/or sleep significantly modulated the variability of ventilation index and Ttot. There were also significant interactions between state and CO2 drive in all respiratory parameters. We conclude that state (sleep or wakefulness) and increased chemical drive affect respiratory variability differentially.