Duration of Sleep Inertia after Napping during Simulated Night Work and in Extended Operations

Due to the mixed findings of previous studies, it is still difficult to provide guidance on how to best manage sleep inertia after waking from naps in operational settings. One of the few factors that can be manipulated is the duration of the nap opportunity. The aim of the present study was to investigate the magnitude and time course of sleep inertia after waking from short (20-, 40- or 60-min) naps during simulated night work and extended operations. In addition, the effect of sleep stage on awakening and duration of slow wave sleep (SWS) on sleep inertia was assessed. Two within-subject protocols were conducted in a controlled laboratory setting. Twenty-four healthy young men (Protocol 1: n?=?12, mean age?=?25.1 yrs; Protocol 2: n?=?12, mean age?=?23.2 yrs) were provided with nap opportunities of 20-, 40-, and 60-min (and a control condition of no nap) ending at 02:00?h after ～20?h of wakefulness (Protocol 1 [P1]: simulated night work) or ending at 12:00?h after ～30?h of wakefulness (Protocol 2 [P2]: simulated extended operations). A 6-min test battery, including the Karolinska Sleepiness Scale (KSS) and the 4-min 2-Back Working Memory Task (WMT), was repeated every 15?min the first hour after waking. Nap sleep was recorded polysomnographically, and in all nap opportunities sleep onset latency was short and sleep efficiency high. Mixed-model analyses of variance (ANOVA) for repeated measures were calculated and included the factors time (time post-nap), nap opportunity (duration of nap provided), order (order in which the four protocols were completed), and the interaction of these terms. Results showed no test x nap opportunity effect (i.e., no effect of sleep inertia) on KSS. However, WMT performance was impaired (slower reaction time, fewer correct responses, and increased omissions) on the first test post-nap, primarily after a 40- or 60-min nap. In P2 only, performance improvement was evident 45?min post-awakening for naps of 40?min or more. In ANOVAs where sleep stage on awakening was included, the test x nap opportunity interaction was significant, but differences were between wake and non-REM Stage 1/Stage 2 or wake and SWS. A further series of ANOVAs showed no effect of the duration of SWS on sleep inertia. The results of this study demonstrate that no more than 15?min is required for performance decrements due to sleep inertia to dissipate after nap opportunities of 60?min or less, but subjective sleepiness is not a reliable indicator of this effect. Under conditions where sleep is short, these findings also suggest that SWS, per se, does not contribute to more severe sleep inertia. When wakefulness is extended and napping occurs at midday (i.e., P2), nap opportunities of 40- and 60-min have the advantage over shorter duration sleep periods, as they result in performance benefits ～45?min after waking.     

Sleep Loss and Performance of Anaesthesia Trainees and Specialists

Fatigue risk associated with work schedules of hospital doctors is coming under increasing scrutiny, with much of the research and regulatory focus on trainees. However, provision of 24 h services involves both trainees and specialists, who have different but interdependent work patterns. This study examined work patterns, sleep (actigraphy, diaries) and performance (psychomotor vigilance task pre‐ and post‐duty) of 28 anaesthesia trainees and 20 specialists across a two‐week work cycle in two urban public hospitals. Trainees at one hospital worked back‐to‐back 12 h shifts, while the others usually worked 9 h day shifts but periodically worked a 14 h day (08:00–22:00 h) to maintain cover until arrival of the night shift (10 h). On 11% of day shifts and 23% of night shifts, trainees were working with ≥2 h of acute sleep loss. However, average sleep loss was not greater on night shifts, possibly because workload at night in one hospital often permitted some sleep. Post‐night shift performance was worse than post‐day shift performance for the median (t₍₁₃₁₎=3.57, p<0.001) and slowest 10% of reaction times (t₍₁₃₄₎=2.91, p<0.01). At the end of night shifts, poorer performance was associated with longer shift length, longer time since waking, greater acute sleep loss, and more total work in the past 24 h. Specialists at both hospitals had scheduled clinical duties during the day and were periodically scheduled on call to cover after‐hours services. On 8% of day shifts and 14% of day+call schedules, specialists were working with ≥2 h of acute sleep loss. They averaged 0.6 h less sleep when working day shifts (t_(23.5)=2.66, p=0.014) and 0.8 h less sleep when working day shifts+call schedules (t_(26.3)=2.65, p=0.013) than on days off. Post‐duty reaction times slowed linearly across consecutive duty days (median reaction time, t₍₁₃₁₎=?3.38, p<0.001; slowest 10%, t₍₁₆₀₎=?3.33, p<0.01; fastest 10%, t₍₁₃₈₎=?2.67, p<0.01). Poorer post‐duty performance was associated with greater acute sleep loss and longer time since waking, but better performance was associated with longer day shifts, consistent with circadian improvement in psychomotor performance across the waking day. This appears to be the first study to document sleep loss among specialist anaesthetists. Consistent with observations from experimental studies, the sleep loss of specialists across 12 consecutive working days was associated with a progressive decline in post‐duty PVT performance. However, this decline occurred with much less sleep restriction (< 1 h per day) than in laboratory studies, suggesting an exacerbating effect of extended wakefulness and/or cumulative fatigue associated with work demands. For both trainees and specialists, robust circadian variation in PVT performance was evident in this complex work setting, despite the potential confounds of variable shift durations and workloads. The relationship between PVT performance of an individual and the safe administration of anaesthesia in the operating theater is unknown. Nevertheless, the findings reinforce that any schedule changes to reduce work‐related fatigue need to consider circadian performance variation and the potential transfer of workload and fatigue risk between trainees and specialists.     

Time-of-Day Mediates the Influences of Extended Wake and Sleep Restriction on Simulated Driving

Although a nonlinear time-of-day and prior wake interaction on performance has been well documented, two recent studies have aimed to incorporate the influences of sleep restriction into this paradigm. Through the use of sleep-restricted forced desynchrony protocols, both studies reported a time-of-day?×?sleep restriction interaction, as well as a time-of-day?×?prior wake?×?sleep dose three-way interaction. The current study aimed to investigate these interactions on simulated driving performance, a more complex task with ecological validity for the problem of fatigued driving. The driving performance of 41 male participants (mean?±?SD: 22.8 ±2.2 yrs) was assessed on a 10-min simulated driving task with the standard deviation of lateral position (SDLAT) measured. Using a between-group design, participants were subjected to either a control condition of 9.33?h of sleep/18.66?h of wake, a moderate sleep-restriction (SR) condition of 7?h of sleep/21?h of wake, or a severe SR condition of 4.66?h of sleep/23.33?h of wake. In each condition, participants were tested at 2.5-h intervals after waking across 7?×?28-h d of forced desynchrony. Driving sessions occurred at nine doses of prior wake, within six divisions of the circadian cycle based on core body temperature (CBT). Mixed-models analyses of variance (ANOVAs) revealed significant main effects of time-of-day, prior wake, sleep debt, and sleep dose on SDLAT. Additionally, significant two-way interactions of time-of-day?×?prior wake and time-of-day?×?sleep debt, as well as significant three-way interactions of time-of-day?×?prior wake?×?sleep debt and time-of-day?×?sleep debt?×?sleep dose were observed. Although limitations such as the presence of practice effects and large standard errors are noted, the study concludes with three findings. The main effects demonstrate that extending wake, reducing sleep, and driving at poor times of day all significantly impair driving performance at an individual level. In addition to this, combining either extended wake or a sleep debt with the early morning hours greatly decreases driving performance. Finally, operating under the influence of a reduced sleep dose can greatly decrease performance at all times of the day. (Author correspondence: raymond.matthews@unisa.edu.au)     

Time Course of Neurobehavioral Alertness During Extended Wakefulness in Morning- and Evening-Type Healthy Sleepers

The aim of the study was to evaluate the influence of chronotype (morning-type versus evening-type) living in a fixed sleep-wake schedule different from one's preferred sleep schedules on the time course of neurobehavioral performance during controlled extended wakefulness. The authors studied 9 morning-type and 9 evening-type healthy male subjects (21.4?±?1.9 yrs). Before the experiment, all participants underwent a fixed sleep-wake schedule mimicking a regular working day (bedtime: 23:30?h; wake time: 07:30?h). Then, following two nights in the laboratory, both chronotypes underwent a 36-h constant routine, performing a cognitive test of sustained attention every hour. Core body temperature, salivary melatonin secretion, objective alertness (maintenance of wakefulness test), and subjective sleepiness (visual analog scale) were also assessed. Evening-types expressed a higher level of subjective sleepiness than morning types, whereas their objective levels of alertness were not different. Cognitive performance in the lapse domain remained stable during the normal waking day and then declined during the biological night, with a similar time course for both chronotypes. Evening types maintained optimal alertness (i.e., 10% fastest reaction time) throughout the night, whereas morning types did not. For both chronotypes, the circadian performance profile was correlated with the circadian subjective somnolence profile and was slightly phase-delayed with melatonin secretion. Circadian performance was less correlated with circadian core body temperature. Lapse domain was phase-delayed with body temperature (2–4?h), whereas optimal alertness was slightly phase-delayed with body temperature (1?h). These results indicate evening types living in a fixed sleep-wake schedule mimicking a regular working day (different from their preferred sleep schedules) express higher subjective sleepiness but can maintain the same level of objective alertness during a normal waking day as morning types. Furthermore, evening types were found to maintain optimal alertness throughout their nighttime, whereas morning types could not. The authors suggest that evening-type subjects have a higher voluntary engagement of wake-maintenance mechanisms during extended wakefulness due to adaptation of their sleep-wake schedule to social constraints. (Author correspondence: jack.taillard@gmail.com)     

Sleep,Sleepiness, Fatigue,and Performance of 12-Hour-Shift Nurses

Nurses working 12-h shifts complain of fatigue and insufficient/poor-quality sleep. Objectively measured sleep times have not been often reported. This study describes sleep, sleepiness, fatigue, and neurobehavioral performance over three consecutive 12-h (day and night) shifts for hospital registered nurses. Sleep (actigraphy), sleepiness (Karolinska Sleepiness Scale [KSS]), and vigilance (Performance Vigilance Task [PVT]), were measured serially in 80 registered nurses (RNs). Occupational fatigue (Occupational Fatigue Exhaustion Recovery Scale [OFER]) was assessed at baseline. Sleep was short (mean 5.5?h) between shifts, with little difference between day shift (5.7?h) and night shift (5.4?h). Sleepiness scores were low overall (3 on a 1–9 scale, with higher score indicating greater sleepiness), with 45% of nurses having high level of sleepiness (score ?>?7) on at least one shift. Nurses were progressively sleepier each shift, and night nurses were sleepier toward the end of the shift compared to the beginning. There was extensive caffeine use, presumably to preserve or improve alertness. Fatigue was high in one-third of nurses, with intershift fatigue (not feeling recovered from previous shift at the start of the next shift) being most prominent. There were no statistically significant differences in mean reaction time between day/night shift, consecutive work shift, and time into shift. Lapsing was traitlike, with rare (39% of sample), moderate (53%), and frequent (8%) lapsers. Nurses accrue a considerable sleep debt while working successive 12-h shifts with accompanying fatigue and sleepiness. Certain nurses appear more vulnerable to sleep loss than others, as measured by attention lapses. (Author correspondence: jgeiger@son.umaryland.edu)     

睡眠剥夺对大鼠行为学及咀嚼肌肌电图的影响

目的：颞下颌关节紊乱病是口腔科的一种常见病和多发病,精神心理因素是颞下颌关节紊乱病的一个主要病因。本文通过观察睡眠剥夺对大鼠行为学及咀嚼肌肌电图的影响,探讨睡眠剥夺在颞下颌关节紊乱病发病中的作用。方法：35只Wistar大鼠,随机分为5组：睡眠剥夺1d组、5d组、9d组、正常对照组和大平台对照组。采用改良多平台睡眠剥夺法（modified multiple plat—formmethod,MMPM）建立大鼠SD模型,观察大鼠行为学及咀嚼肌肌电图的变化。结果：睡眠剥夺1d组和5d组在旷场实验水平得分和垂直得分上均高于对照组,而睡眠剥夺9d组均低于对照组;睡眠剥夺1d、5d和9d组在松弛状态和紧咬状态时颞肌前后束及咬肌的电位均明显高于对照组,且两侧无明显差别,同时,睡眠剥夺组双侧颞肌和咬肌的肌电图静息期较对照组显著延长。结论：睡眠剥夺可使大鼠行为学发生改变并对咀嚼肌肌电图造成影响,这可能是颞下颌关节紊乱病的病因之一,为我们对颞下颌关节紊乱病的预防和治疗提供了一定的理论指导。     

Neurophysiologic measurement of continuity in the sleep of fetuses during the last week of pregnancy and in newborns

Our aim was to measure the correlation between fetal electrocardiographic (FECG) recordings of low-risk pregnancies and polysomnographic (PSG) study parameters in low-risk infants born at term as a measurement of perinatal sleep-development continuity.We designed a short, prospective, observational follow-up of physiologic parameters between fetuses and newborns. We studied 10 fetuses from low-risk pregnant female out-patients and the same subjects as low-risk newborns delivered at term. Fetal state (FS) was defined in FECG recordings reassembling the following: fetal state I (quiet sleep or QS); fetal state II (active sleep or AS); fetal state III (quiet waking), and fetal state IV (active waking). Percentages of AS, QS, and wakefulness in PSG studies of newborns were also determined.Comparisons of FS I with QS showed a significant reduction in QS, while comparison of FS II with AS showed significant reduction in AS. Negative correlations were found between FS I with QS, and FS II with AS. Number of cycles in FECG recordings and PSG sleep cycles also demonstrated significant correlation.In conclusion our data showed partial but significant sleep function continuity from fetal to neonatal period.     

Sleep,Sleepiness, and Neurobehavioral Performance While on Watch in a Simulated 4 Hours on/8 Hours off Maritime Watch System

Seafarer sleepiness jeopardizes safety at sea and has been documented as a direct or contributing factor in many maritime accidents. This study investigates sleep, sleepiness, and neurobehavioral performance in a simulated 4?h on/8?h off watch system as well as the effects of a single free watch disturbance, simulating a condition of overtime work, resulting in 16?h of work in a row and a missed sleep opportunity. Thirty bridge officers (age 30?±?6 yrs; 29 men) participated in bridge simulator trials on an identical 1-wk voyage in the North Sea and English Channel. The three watch teams started respectively with the 00–04, the 04–08, and the 08–12 watches. Participants rated their sleepiness every hour (Karolinska Sleepiness Scale [KSS]) and carried out a 5-min psychomotor vigilance test (PVT) test at the start and end of every watch. Polysomnography (PSG) was recorded during 6 watches in the first and the second half of the week. KSS was higher during the first (mean?±?SD: 4.0?±?0.2) compared with the second (3.3?±?0.2) watch of the day (p?<?0.001). In addition, it increased with hours on watch (p?<?0.001), peaking at the end of watch (4.1?±?0.2). The free watch disturbance increased KSS profoundly (p?<?0.001): from 4.2?±?0.2 to 6.5?±?0.3. PVT reaction times were slower during the first (290?±?6?ms) compared with the second (280?±?6?ms) watch of the day (p?<?0.001) as well as at the end of the watch (289?±?6?ms) compared with the start (281?±?6?ms; p?=?0.001). The free watch disturbance increased reaction times (p?<?0.001) from 283?±?5 to 306?±?7?ms. Similar effects were observed for PVT lapses. One third of all participants slept during at least one of the PSG watches. Sleep on watch was most abundant in the team working 00–04 and it increased following the free watch disturbance. This study reveals that—within a 4?h on/8?h off shift system—subjective and objective sleepiness peak during the night and early morning watches, coinciding with a time frame in which relatively many maritime accidents occur. In addition, we showed that overtime work strongly increases sleepiness. Finally, a striking amount of participants fell asleep while on duty.     

Premarin improves memory, prevents scopolamine-induced amnesia and increases number of basal forebrain choline acetyltransferase positive cells in middle-aged surgically menopausal rats

Conjugated equine estrogen (CEE) is the most commonly prescribed estrogen therapy, and is the estrogen used in the Women's Health Initiative study. While in-vitro studies suggest that CEE is neuroprotective, no study has evaluated CEE's effects on a cognitive battery and brain immunohistochemistry in an animal model. The current experiment tested whether CEE impacted: I) spatial learning, reference memory, working memory and long-term retention, as well as ability to handle mnemonic delay and interference challenges; and, II) the cholinergic system, via pharmacological challenge during memory testing and ChAT-immunoreactive cell counts in the basal forebrain. Middle-aged ovariectomized (Ovx) rats received chronic cyclic injections of either Oil (vehicle), CEE-Low (10 μg), CEE-Medium (20 μg) or CEE-High (30 μg) treatment. Relative to the Oil group, all three CEE groups showed less overnight forgetting on the spatial reference memory task, and the CEE-High group had enhanced platform localization during the probe trial. All CEE groups exhibited enhanced learning on the spatial working memory task, and CEE dose-dependently protected against scopolamine-induced amnesia with every rat receiving the highest CEE dose maintaining zero errors after scopolamine challenge. CEE also increased number of ChAT-immunoreactive neurons in the vertical diagonal band of the basal forebrain. Neither the ability to remember after a delay nor interference, nor long-term retention, was influenced by the CEE regimen used in this study. These findings are similar to those reported previously for 17 β-estradiol, and suggest that CEE can provide cognitive benefits on spatial learning, reference and working memory, possibly through cholinergic mechanisms.     

A study of visuospatial working memory pre- and post-Gonadotropin Hormone Releasing Hormone agonists (GnRHa) in young women

Gonadotropin Hormone Releasing Hormone agonists (GnRHa) produce an acute decline in ovarian hormone production leading to a ‘pseudo’ menopause. This is therapeutically useful in the management of a variety of gynaecological conditions but also serves as a powerful model to study the effects of ovarian hormones on cognition. Animal and human behavioral studies report that memory is particularly sensitive to the effects ovarian hormone suppression (e.g. post GnRHa). Further, it has recently been reported that ovariectomy in young women increases the risk of cognitive impairment in later life. However, the underlying brain networks and/or stages of memory processing that might be modulated by acute ovarian hormone suppression remain poorly understood. We used event-related fMRI to examine the effect of GnRHa on visual working memory (VWM). Neuroimaging outcomes from 17 pre-menopausal healthy women were assessed at baseline and 8 weeks after GnRHa treatment. Seventeen matched wait-listed volunteers served as the control group and were assessed at similar intervals during the late follicular phase of the menstrual cycle. We report GnRHa was associated with attenuation of left parahippocampal (BA 35) and middle temporal gyri (BA 21 ,22, 39) activation, with a significant group-by-time interaction at left precuneus (BA 7) and posterior cingulate cortex (PCC) (BA 31) at encoding, and with cerebellar activation at recognition in the context of unimpaired behavioral responses. Our study suggests that acute ovarian hormone withdrawal following GnRHa, and perhaps at other times, (e.g. following surgical menopause and postpartum) alters the neural circuitry underlying performance of VWM.     

Spousal bereavement and the cognitive health of older adults in the US: New insights on channels,single items,and subjective evidence

This study provides novel insights into older adults’ cognitive functioning before and after widowhood onset and possible effect channels. It further examines gender heterogeneity in the adaptation to (anticipated or actual) spousal bereavement, comparing objective evidence with subjective evidence of cognitive abilities. We used longitudinal data of up to 26,584 participants of the Health and Retirement Study, aged over 50 at recruitment, assessed biennially between 1998 and 2016. Two-way fixed effects with dynamic treatment effects were estimated for various cognitive measures, including six aggregated indices and six single item scales. After adjusting for effect channels including depression, social vulnerability, and stress, there remained significant widowhood effects on older adults’ cognitive health. Using single item scales, we established the adverse contemporaneous and adaptation effects on bereaved older females’ short-term memory, semantic memory, and numeracy. For bereaved older males, working memory and focus-of-attention deteriorated after widowhood onset. Meanwhile, subjective memory rating remained intact, contrary to objective evidence. We conclude that cognitive transitions to and from widowhood can exhibit distinctive patterns across objective and subjective cognitive domains. With the effect channels in mind, cognitive intervention for widowed older adults should be tailored to the temporal distance to spousal loss, gender, and task.     

慢性束缚应激对SD和Wistar大鼠学习记忆能力的影响

目的探讨慢性束缚应激对Wistar、SD两种品系大鼠学习记忆能力的影响,为应激模型中实验动物的选择提供依据。方法对两种品系大鼠(Wistar、SD)采用每天束缚10 h,束缚28 d建立慢性应激模型。采用物体认知新物体识别实验和Morris水迷宫空间学习、工作记忆行为学检测方法,观察束缚应激对两种品系实验动物学习记忆能力的影响。结果束缚28 d后,物体识别实验中,Wistar、SD模型组的辨别指数(discrimination index,DI)均低于对照组,但只有SD两组间差异存在显著性(P0.05);水迷宫空间学习阶段,SD模型组潜伏期高于对照组,第5天差异有显著性(P0.05),而Wistar模型组与对照组间的潜伏期没有差异;水迷宫工作记忆阶段,SD大鼠模型组与正常组比较,潜伏期显著增加(P0.05),Wistar模型大鼠的潜伏期与对照组比较没有显著差异。结论新物体识别实验和水迷宫实验,这两种反应动物不同学习记忆能力的行为学实验结果都表明,慢性束缚应激(10 h,28 d)对SD大鼠学习记忆能力的损伤较Wistar大鼠明显。SD大鼠可能更适合作为慢性应激所致学习记忆损伤动物模型。     

The Effects of a Nap Opportunity in Quiet and Noisy Environments on Driving Performance

While napping has previously been shown to alleviate the effects of sleep loss, before advocating the use of naps in transport accident campaigns it is necessary to consider whether a nap opportunity in a noisy uncomfortable environment can produce the same benefits as a nap opportunity in conditions that are conducive to sleep. To examine this, eight participants drove a driving simulator for 50 min at 11:00 h on three different test days. The simulator used has previously been found to be sensitive to the effects of sleep loss, alcohol consumption, and time of day. All three sessions were conducted after one night of sleep loss. Prior to driving during each session the participants either had a 60 min nap opportunity in a quiet or noisy environment, or no nap opportunity. Driving performance and reaction time while driving were measured, as were subjective sleepiness and ratings of sleep quality. No significant benefits of nap opportunities on driving performance were found. Levels of subjective sleepiness were not affected by the nap opportunity condition; however, sleep was rated as more refreshing and restful after a nap in a quiet environment compared to noisy environment. The measures of effect size reported suggest further research is required to unequivocally test the effects of nap opportunities on driving ability.     

The Effect of One Night's Sleep Deprivation on Temperature,Mood, and Physical Performance in Subjects with Different Amounts of Habitual Physical Activity

Eleven healthy males were studied twice. On one occasion (control, C), they slept (night 1) and then underwent a battery of tests at 4h intervals from 06: 00 day 1 to 02: 00 day 2; then, after a normal sleep (night 2), they were tested from 10: 00 to 22: 00 on day 2. On the second occasion (sleep deprivation, SD), the subjects remained awake during night 1. Each battery of tests consisted of measurements of tympanic membrane temperature, profile of mood states (POMS), muscle strength, self-chosen work rate (SCWR), perceived exertion, and heart rate (HR) while exercising on a stationary cycle ergometer. Subjects also kept a diary of their activities during the two days and answered a questionnaire about their habitual physical activity. Results showed a significant negative effect of sleep deprivation on most mood states on day 1, but no effect on the other variables. By day 2, mood had tended to recover, though muscle strength tended to be worse in both control and sleep-deprivation experiments. There was also a more general tendency for negative effects to be present at the end of day 1 (02: 00) or at the beginning of day 2 (10: 00). There was limited support for the view that subjects who were habitually more active showed less negative effects after sleep deprivation and responded less adversely to the poor sleep achieved on the university premises (night 2). These results stress the considerable interindividual variation in the responses to sleep loss and, therefore, the difficulty associated with giving general advice to individuals about work or training capability after sleep loss.     

Effects of Acute Lorazepam Administration on Aminergic Activity in Normal Elderly Subjects: Relationship to Performance Effects and Apolipoprotein Genotype

The effects of acute lorazepam challenges on plasma (p) HVA, MHPG, and 5-HIAA, and their relationship to drug-induced cognitive and motor deficits and the apolipoprotein (APOE)-epsilon4 allele were examined. Eighteen healthy elderly (8 epsilon4 carriers) received placebo or acute oral lorazepam doses (0.5 mg or 1 mg) in random sequence, 1-week apart. Cognitive assessment and plasma levels of pHVA, pMHPG, and p5-HIAA were determined at baseline and at 1, 2.5, and 5 h postchallenge. There was no drug-to-placebo difference in monoamine levels and no consistent relationship between changes in monoamine levels and cognitive performance, regardless of epsilon4 status. However, the 1.0 mg dose increased p5-HIAA in epsilon4 carriers, whereas it caused a reduction in noncarriers. Higher baseline pMHPG and p5-HIAA levels were associated with better baseline memory. The epsilon4 allele may modulate the effect of lorazepam on p5-HIAA, but further studies are needed to confirm this finding and elucidate its possible significance.     

Dose dependent effects of oxytocin on cognitive defects and anxiety disorders in adult rats following acute infantile maternal deprivation stress

ABSTRACT

Maternal deprivation at an early age is a powerful stressor that causes permanent alterations in cognitive and behavioral functions during the later stages of life. We investigated the effects of oxytocin on cognitive defects and anxiety disorders caused by acute infantile maternal deprivation in adult rats. We used 18-day-old Wistar albino rats of both sexes. The experimental groups included control (C), maternally deprived (MD), maternally deprived and treated with 0.02 μg/kg oxytocin (MD-0.02 µg/kg oxy), maternally deprived and treated with 2 μg/kg oxytocin (MD-2 µg/kg oxy). When the rats were 60 days old, the open field (OF) and elevated plus maze (EPM) behavioral tests, and the Morris water maze (MWM) test for spatial learning and memory were performed. In addition, the number of neurons in the hippocampus, prefrontal cortex (PFC) and amygdala were determined using quantitative histology. We also measured vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF) levels in the PFC. In both sexes, the MD group failed the learning test and the MD-2 μg/kg oxy group failed in the memory test. The MD-0.02 μg/kg oxy group spent more time in the open arm of the EPM device and their locomotor activities were greater in the OF test. The VEGF and BDNF levels in the PFC were higher in the MD-0.02 μg/kg oxy groups than the other maternally deprived groups (oxytocin ±). The number of PFC neurons was low in all male maternally deprived (oxytocin ±) groups, while the number of amygdala neurons was low in both female and male maternally deprived (oxytocin ±) groups. Male rats were more affected by maternal deprivation; administration of oxytocin had dose-dependent biphasic effects on learning, memory and anxiety.