The effect of Benson's relaxation response on sleep quality and anorexia in cancer patients undergoing chemotherapy: A randomized controlled trial.

BACKGROUND AND OBJECTIVES: Patients with cancer experience many side effects due to its nature and usual treatments. Sleep disorders and anorexia are the most commonly reported symptoms in cancer patients undergoing chemotherapy. The present study aimed to investigate the effect of Benson's Relaxation Response (BRR) on sleep quality and anorexia in cancer patients undergoing chemotherapy. METHODOLOGY AND PARTICIPANTS: In the present clinical trial, a total of 84 patients were enrolled and randomly divided into two groups of experimental and control. Benson's relaxation response was administered to the experimental group twice a day over 5 consecutive days. Data was collected using St. Mary's Hospital Sleep Questionnaire (SMHSQ) and anorexia questionnaire with Visual Analog Scale (VAS). RESULTS: The results of our study showed a significant improvement in the sleep quality in the experimental group at 24 (p = 0.02) and 48 (p = 0.001) hours after the intervention compared to the control group. Benson's relaxation response (BRR) also had a significant effect on the anorexia in the experimental group at 24 (7.5 ± 1.6) and 48 (6.9 ± 2.1) hours after the intervention compared to the control group. No side effects were reported during the study and follow-up period. CONCLUSION: Benson's relaxation response as a complementary method may improve sleep quality and anorexia in cancer patients undergoing chemotherapy. Further studies with greater sample size and longer follow-up period are needed to confirm the current findings.

Impact of a patient-tailored complementary/integrative medicine programme on disturbed sleep quality among patients undergoing chemotherapy.

OBJECTIVES: The present study examined the impact of a patient-tailored complementary/integrative medicine (CIM) programme on sleep quality in patients undergoing chemotherapy for breast and gynaecological cancer. METHODS: Study participants received standard supportive care, with or without weekly CIM treatments. Disturbed sleep quality was defined as a score of ≥4 on the Edmonton Symptom Assessment Scale (ESAS) or a score of ≥3 on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). Adherence to integrative care was defined as attending ≥4 CIM treatments, with ≤30 days between each session. RESULTS: Of 388 eligible patients, 264 (68%) reported disturbed sleep quality. Baseline-to-follow up assessment (at 6 weeks) was optimal for 104 patients in the treatment group and for 76 controls, with 75 of treated patients found to be adherent to the CIM intervention. Sleep-related ESAS scores improved more significantly in treated patients (p=0.008), as did sleep-related concerns on EORTC (treatment group, p=0.026). CONCLUSIONS: A patient-tailored CIM programme may improve sleep quality and related concerns among patients with breast and gynaecological cancer undergoing chemotherapy. Further research is needed to better understand the impact of CIM on sleep quality in this patient population. TRIAL REGISTRATION NUMBER: NCT01860365.

Disruption of sleep, sleep-wake activity rhythm, and nocturnal melatonin production in breast cancer patients undergoing adjuvant chemotherapy: prospective cohort study.

OBJECTIVE: This prospective cohort study captured the patterns of sleep, sleep-wake activity rhythm, and first-morning urinary melatonin in breast cancer patients undergoing adjuvant chemotherapy. METHODS: Breast cancer patients undergoing adjuvant chemotherapy wore wrist actigraph for 168 h and collected first-morning void urine samples before treatment, during the first, and at the last cycle of chemotherapy. We converted actigraphy data into sleep duration, sleep efficiency, nighttime total wake time, percent rhythm, F-statistic, amplitude, mesor, and acrophase. We then assessed urinary 6-sulfatoxymelatonin (aMT6s) levels. RESULTS: This cohort contained 180 participants. Compared with the baseline, sleep efficiency during the first and last cycle decreased by 10.16% [95% confidence interval (95% CI): 5.85%, 14.47%] and 5.01% (95% CI: 0.50%, 9.53%), respectively. Similarly, percent rhythm decreased by 27.20% (95% CI: 19.95%, 34.45%) during the first cycle and 21.20% (95% CI: 13.52, 28.89) during the last cycle. Taking the baseline as the reference, aMT6s levels during the first and last cycle decreased by 11.27% (95% CI: 0.37%, 22.16%) and 14.74% (95% CI: 2.34, 27.11), respectively. CONCLUSION: The first administration of adjuvant chemotherapy is associated with sleep disturbance and sleep-wake activity rhythm disruption among breast cancer patients, while the disturbance and disruption during the last cycle are less severe; nevertheless, repeated administration of chemotherapy results in progressive impairment of nocturnal melatonin production.

Phase I dose-finding study for melatonin in pediatric oncology patients with relapsed solid tumors.

BACKGROUND: Melatonin is a natural health product used for sleep disturbances. In preliminary studies of adults with advanced cancer, 20 mg of melatonin daily was associated with reduction in anorexia and weight loss-symptoms that also impact pediatric oncology patients. High doses of melatonin have not been studied in pediatrics. METHODS: This was a multicenter single-arm phase I dose-escalation study utilizing a 3 + 3 design to determine the safety and tolerability of escalating doses of melatonin in pediatric oncology patients with relapsed solid tumors. Melatonin was given for 8 weeks at three dose levels-0.075 mg/kg (maximum 5 mg), 0.15 mg/kg (maximum 10 mg), and 0.3 mg/kg (maximum 20 mg). RESULTS: Melatonin was well tolerated at all three dose levels with no significant adverse events or dose-limiting toxicities. The only grade 3/4 toxicities were myelosuppression, which was attributed to the concomitant chemotherapy and occurred at all dose levels. Weight gain occurred in seven of nine patients, with a median increase of 1.1 kg (range -3.3 to 4.5) or 3.4% (range -10.2 to 8.7), with two patients losing weight (one in dose level 1 and one level 3). CONCLUSIONS: Melatonin is well tolerated at a dose of 0.3 mg/kg (maximum 20 mg), in the pediatric population. This study provides the background for further study of high-dose melatonin in pediatric oncology patients.

Sleep spindles and slow waves in schizophrenia and related disorders: main findings, challenges and future perspectives.

Sleep abnormalities have recently gained renewed attention in patients diagnosed with schizophrenia. Disrupted thalamocortical brain oscillations hold promise as putative biomarkers or endophenotypes of the disorder. Despite an increase in studies related to sleep spindle and slow-wave activity, findings remain in part contradictory. Although sleep spindle deficits have been confirmed in several groups of patients with chronic, medicated schizophrenia, data on the early stages of the disorder and in unmedicated subjects are still insufficient. Findings on slow-wave abnormalities are largely inconclusive, possibly due to the different criteria employed to define the phenomenon and to the influence of atypical antipsychotics. In this review, we aim to address the methodological and practical issues that may have limited the consistency of findings across research groups and different patient populations. Given the neurobiological relevance of these oscillations, which reflect the integrity of thalamocortical and cortico-cortical function, research in this domain should be encouraged. To promote widespread consensus over the scientific and clinical implications of these sleep-related phenomena, we advocate uniform and sound methodological approaches. These should encompass electroencephalographic recording and analysis techniques but also selection criteria and characterization of clinical populations.

Randomized trial of Tibetan yoga in patients with breast cancer undergoing chemotherapy.

BACKGROUND: The current randomized trial examined the effects of a Tibetan yoga program (TYP) versus a stretching program (STP) and usual care (UC) on sleep and fatigue in women with breast cancer who were undergoing chemotherapy. METHODS: Women with stage (American Joint Committee on Cancer (AJCC) TNM) I to III breast cancer who were undergoing chemotherapy were randomized to TYP (74 women), STP (68 women), or UC (85 women). Participants in the TYP and STP groups participated in 4 sessions during chemotherapy, followed by 3 booster sessions over the subsequent 6 months, and were encouraged to practice at home. Self-report measures of sleep disturbances (Pittsburgh Sleep Quality Index), fatigue (Brief Fatigue Inventory), and actigraphy were collected at baseline; 1 week after treatment; and at 3, 6, and 12 months. RESULTS: There were no group differences noted in total sleep disturbances or fatigue levels over time. However, patients in the TYP group reported fewer daily disturbances 1 week after treatment compared with those in the STP (difference, -0.43; 95% confidence interval [95% CI], -0.82 to -0.04 [P = .03]) and UC (difference, -0.41; 95% CI, -0.77 to -0.05 [P = .02]) groups. Group differences at the other time points were maintained for TYP versus STP. Actigraphy data revealed greater minutes awake after sleep onset for patients in the STP group 1 week after treatment versus those in the TYP (difference, 15.36; 95% CI, 7.25-23.48 [P = .0003]) and UC (difference, 14.48; 95% CI, 7.09-21.87 [P = .0002]) groups. Patients in the TYP group who practiced at least 2 times a week during follow-up reported better Pittsburgh Sleep Quality Index and actigraphy outcomes at 3 months and 6 months after treatment compared with those who did not and better outcomes compared with those in the UC group. CONCLUSIONS: Participating in TYP during chemotherapy resulted in modest short-term benefits in sleep quality, with long-term benefits emerging over time for those who practiced TYP at least 2 times a week. Cancer 2018;124:36-45. © 2017 American Cancer Society.

Dexamethasone Chemotherapy Does Not Disrupt Orexin Signaling.

BACKGROUND: Steroid-induced sleep disturbance is a common and highly distressing morbidity for children receiving steroid chemotherapy for the treatment of pediatric acute lymphoblastic leukemia (ALL). Sleep disturbance can negatively impact overall quality of life, neurodevelopment, memory consolidation, and wound healing. Hypothalamic orexin neurons are influential wake-promoting neurons, and disturbances in orexin signaling leads to abnormal sleep behavior. A new class of drug, the orexin receptor antagonists, could be an intriguing option for sleep disorders caused by increased orexinergic output. Our aim was to examine the impact of ALL treatment doses of corticosteroids on the orexin system in rodents and in children undergoing treatment for childhood ALL. METHODS: We administered repeated injections of dexamethasone to rodents and measured responsive orexin neural activity compared to controls. In children with newly diagnosed standard risk B-cell ALL receiving dexamethasone therapy per Children's Oncology Group (COG) induction therapy from 2014-2016, we collected pre- and during-steroids matched CSF samples and measured the impact of steroids on CSF orexin concentration. RESULTS: In both rodents, all markers orexin signaling, including orexin neural output and orexin receptor expression, were preserved in the setting of dexamethasone. Additionally, we did not detect a difference in pre- and during-dexamethasone CSF orexin concentrations in children receiving dexamethasone. CONCLUSIONS: Our results demonstrate that rodent and human orexin physiology is largely preserved in the setting of high dose dexamethasone. The data obtained in our experimental model fail to demonstrate a causative role for disruption of the orexin pathway in steroid-induced sleep disturbance.

Sleep disturbances and neurotoxicity in workers exposed to hydrocarbons. An observational study from Algeria.

BACKGROUND: Occupational exposure to solvents may lead to neurotoxicity and sleep disturbances. We aimed to investigate the association of occupational exposure to petroleum-derived hydrocarbons with neurotoxicity and sleep disturbance symptoms. METHODS: We included male workers handling/distributing petroleum products (exposed, n = 250) and electricians (non-exposed, n = 250) from two companies in Tlemcen (Algeria). Neurotoxicity was evaluated with the Q-16 questionnaire, and sleep disturbances with the Epworth and the Berlin questionnaires. Multivariable Poisson regression models with robust error variances were applied obtaining risk ratios (RR) and their 95% confidence interval (CI). RESULTS: Overall, the prevalence of reported neurotoxicity and sleep disturbance symptoms was higher in exposed than in non-exposed workers. Significant adjusted associations were observed for neurotoxicity, snoring, and excessive sleepiness (RR = 2.2, CI: 1.7-2.8; RR = 1.4; CI: 1.1-1.7; RR = 1.3, CI: 1.2-1.5, respectively). No significant associations were observed with the Epworth score. CONCLUSIONS: Our questionnaire-based cross-sectional study suggests that exposure to petroleum-derived hydrocarbons is associated with self-reported sleep disturbances and neurotoxicity symptoms.

Glucocorticoid receptors in the locus coeruleus mediate sleep disorders caused by repeated corticosterone treatment.

Stress induced constant increase of cortisol level may lead to sleep disorder, but the mechanism remains unclear. Here we described a novel model to investigate stress mimicked sleep disorders induced by repetitive administration of corticosterone (CORT). After 7 days treatment of CORT, rats showed significant sleep disturbance, meanwhile, the glucocorticoid receptor (GR) level was notably lowered in locus coeruleus (LC). We further discovered the activation of noradrenergic neuron in LC, the suppression of GABAergic neuron in ventrolateral preoptic area (VLPO), the remarkable elevation of norepinephrine in LC, VLPO and hypothalamus, as well as increase of tyrosine hydroxylase in LC and decrease of glutamic acid decarboxylase in VLPO after CORT treatment. Microinjection of GR antagonist RU486 into LC reversed the CORT-induced sleep changes. These results suggest that GR in LC may play a key role in stress-related sleep disorders and support the hypothesis that repeated CORT treatment may decrease GR levels and induce the activation of noradrenergic neurons in LC, consequently inhibit GABAergic neurons in VLPO and result in sleep disorders. Our findings provide novel insights into the effect of stress-inducing agent CORT on sleep and GRs' role in sleep regulation.

Sleep symptoms associated with intake of specific dietary nutrients.

Sleep symptoms are associated with weight gain and cardiometabolic disease. The potential role of diet has been largely unexplored. Data from the 2007-2008 National Health and Nutrition Examination Survey (NHANES) were used (n = 4552) to determine which nutrients were associated with sleep symptoms in a nationally representative sample. Survey items assessed difficulty falling asleep, sleep maintenance difficulties, non-restorative sleep and daytime sleepiness. Analyses were adjusted for energy intake, other dietary factors, exercise, body mass index (BMI) and sociodemographics. Population-weighted, logistic regression, with backwards-stepwise selection, examined which nutrients were associated with sleep symptoms. Odds ratios (ORs) reflect the difference in odds of sleep symptoms associated with a doubling in nutrient. Nutrients that were associated independently with difficulty falling asleep included (in order): alpha-carotene (OR = 0.96), selenium (OR = 0.80), dodecanoic acid (OR = 0.91), calcium (OR = 0.83) and hexadecanoic acid (OR = 1.10). Nutrients that were associated independently with sleep maintenance difficulties included: salt (OR = 1.19), butanoic acid (0.81), carbohydrate (OR = 0.71), dodecanoic acid (OR = 0.90), vitamin D (OR = 0.84), lycopene (OR = 0.98), hexanoic acid (OR = 1.25) and moisture (OR = 1.27). Nutrients that were associated independently with non-restorative sleep included butanoic acid (OR = 1.09), calcium (OR = 0.81), vitamin C (OR = 0.92), water (OR = 0.98), moisture (OR = 1.41) and cholesterol (OR = 1.10). Nutrients that were associated independently with sleepiness included: moisture (OR = 1.20), theobromine (OR = 1.04), potassium (OR = 0.70) and water (OR = 0.97). These results suggest novel associations between sleep symptoms and diet/metabolism, potentially explaining associations between sleep and cardiometabolic diseases.

'Ecstasy' and the use of sleep medications in a general community sample: a 4-year follow-up.

AIMS: Animal models show that a single dose of 3,4-methylenedioxymethamhetamine (MDMA; 'ecstasy') can result in long-term disruption of sleep. We evaluated the relationship between ecstasy consumption and the use of sleep medications in humans after controlling for key factors. DESIGN: The Personality and Total Health Through Life project uses a longitudinal cohort with follow-up every 4 years. This study reports data from waves 2 and 3. SETTING: Participants were recruited from the electoral roll in the Australian Capital Territory and Queanbeyan, New South Wales, Australia. PARTICIPANTS: Participants were aged 20-24 years at wave 1 (1999-2000). MEASURES: The study collected self-reported data on ecstasy, meth/amphetamine, cannabis, alcohol, tobacco and use of sleeping medications (pharmaceutical or other substances). Depression was categorized using the Brief Patient Health Questionnaire (BPHQ). Other psychosocial measures included life-time traumas. We used generalized estimating equations to model outcomes. FINDINGS: Ecstasy data were available from 2128 people at wave 2 and 1977 at wave 3: sleeping medication use was reported by 227 (10.7%) respondents at wave 2 and 239 (12.1%) at wave 3. Increased odds ratios (OR) for sleeping medication use was found for those with depression [OR = 1.88, 95% confidence interval (CI): 1.39, 2.53], women (OR = 1.44, 95% CI: 1.13, 1.84), and increased by 19% for each life-time trauma. Ecstasy use was not a significant predictor, but ≥monthly versus never meth/amphetamine use increased the odds (OR = 3.03, 95% CI 1.30, 7.03). CONCLUSION: The use of ecstasy appears to be associated with the use of sleeping medications but this association can be accounted for by other factors.

A human laboratory study investigating the effects of quetiapine on marijuana withdrawal and relapse in daily marijuana smokers.

Marijuana withdrawal contributes to the high relapse rates in individuals seeking treatment for marijuana-use disorders. Quetiapine, an atypical antipsychotic, reduces characteristic symptoms of marijuana withdrawal in a variety of psychiatric conditions, including mood lability, sleep disruption and anorexia. This human laboratory study investigated the effectiveness of quetiapine to decrease marijuana withdrawal and relapse to marijuana use in non-treatment-seeking marijuana smokers. Volunteers were maintained on placebo or quetiapine (200 mg/day) in this double-blind, counter-balanced, within-subject study consisting of two 15-day medication phases, the last 8 days of which were in-patient. On the first in-patient day, active marijuana [6.2% delta (9)-tetrahydrocannabinol (THC)] was repeatedly smoked under controlled conditions. For the next 3 days, inactive marijuana (0.0% THC) was available for self-administration (withdrawal). On the subsequent 4 days, active marijuana (6.2% THC) was available for self-administration (relapse). Volunteers (n = 14) who smoked an average of 10 marijuana cigarettes/day, 7 days/week, completed the study. Under placebo, withdrawal was marked by increased subjective ratings of negative mood, decreased sleep quality, and decreased caloric intake and weight loss. Compared with placebo, quetiapine improved sleep quality, increased caloric intake and decreased weight loss. However, quetiapine increased marijuana craving and marijuana self-administration during the relapse phase. These data do not suggest that quetiapine shows promise as a potential treatment for marijuana dependence.

Characterization of individuals seeking treatment for caffeine dependence.

Previous investigations have identified individuals who meet criteria for Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.; DSM-IV-TR; American Psychiatric Association, 2000) substance dependence as applied to caffeine, but there is little research on treatments for caffeine dependence. This study aimed to thoroughly characterize individuals who are seeking treatment for problematic caffeine use. Ninety-four individuals who identified as being psychologically or physically dependent on caffeine, or who had tried unsuccessfully to modify caffeine consumption participated in a face-to-face diagnostic clinical interview. They also completed measures concerning caffeine use and quitting history, reasons for seeking treatment, and standardized self-report measures of psychological functioning. Caffeine treatment seekers (mean age 41 years, 55% women) consumed an average of 548 mg caffeine per day. The primary source of caffeine was coffee for 50% of the sample and soft drinks for 37%. Eighty-eight percent reported prior serious attempts to modify caffeine use (mean 2.7 prior attempts), and 43% reported being advised by a medical professional to reduce or eliminate caffeine. Ninety-three percent met criteria for caffeine dependence when generic DSM-IV-TR substance dependence criteria were applied to caffeine use. The most commonly endorsed criteria were withdrawal (96%), persistent desire or unsuccessful efforts to control use (89%), and use despite knowledge of physical or psychological problems caused by caffeine (87%). The most common reasons for wanting to modify caffeine use were health-related (59%) and not wanting to be dependent on caffeine (35%). This investigation reveals that there are individuals with problematic caffeine use who are seeking treatment and suggests that there is a need for effective caffeine dependence treatments.

Black cohosh (Cimicifuga racemosa) in tamoxifen-treated breast cancer patients with climacteric complaints - a prospective observational study.

OBJECTIVE: The antihormonal therapy of breast cancer patients with the antiestrogen tamoxifen often induces or aggravates menopausal complaints. As estrogen substitution is contraindicated, herbal alternatives, e.g. extracts of black cohosh are often used. DESIGN: A prospective observational study was carried out in 50 breast cancer patients with tamoxifen treatment. All patients had had surgery, most of them had undergone radiation therapy (87%) and approximately 50% had received chemotherapy. Every patient was treated with an isopropanolic extract of black cohosh (1-4 tablets, 2.5 mg) for 6 months. Patients recorded their complaints before therapy and after 1, 3, and 6 months of therapy using the menopause rating scale (MRS II). RESULTS: The reduction of the total MRS II score under black cohosh treatment from 17.6 to 13.6 was statistically significant. Hot flashes, sweating, sleep problems, and anxiety improved, whereas urogenital and musculoskeletal complaints did not change. In all, 22 patients reported adverse events, none of which were linked with the study medication; 90% reported the tolerability of the black cohosh extract as very good or good. CONCLUSIONS: Black cohosh extract seems to be a reasonable treatment approach in tamoxifen treated breast cancer patients with predominantly psychovegetative symptoms.

GABAA receptors in the thalamus: alpha4 subunit expression and alcohol sensitivity.

The inhibitory neurotransmitter gamma-aminobutyric acid (GABA) has long been implicated in the anxiolytic, amnesic, and sedative behavioral effects of alcohol. A large number of studies have investigated the interactions of alcohol with GABA receptors. Many investigators have reported effects of "high concentrations" (50-100 mM) of alcohol on GABA-mediated synaptic inhibition, but effects of the "low concentrations" (1-30 mM) of alcohol normally associated with mild intoxication have been elusive until recently. A novel form of "tonic inhibition" has been described in the central nervous system (CNS) that is generated by the persistent activation of extrasynaptic gamma-aminobutyric acid type A receptors (GABAA-Rs). These receptors are specific GABAA-R subtypes and distinct from the synaptic subtypes. Tonic inhibition regulates the excitability of individual neurons and the activity and rhythmicity of neural networks. Interestingly, several reports show that tonic inhibition is sensitive to low concentrations of alcohol. The thalamus is a structure that is critically important in the control of sleep and wakefulness. GABAergic inhibition in the thalamus plays a crucial role in the generation of sleep waves. Among the various GABAA-R subunits, the alpha1, alpha4, beta2, and delta subunits are heavily expressed in thalamic relay nuclei. Tonic inhibition has been demonstrated in thalamocortical relay neurons, where it is mediated by alpha4beta2delta GABAA-Rs. These extrasynaptic receptors are highly sensitive to gaboxadol, a novel hypnotic, but insensitive to benzodiazepines. Tonic inhibition is absent in thalamic relay neurons from alpha4 knockout mice, as are the sedative and analgesic effects of gaboxadol. The sedative effects of alcohol can promote sleep. However, alcohol also disrupts the normal sleep pattern and reduces sleep quality. As a result, sleep disturbance caused by alcohol can play a role in the progression of alcoholism. As an important regulator of sleep cycles, inhibition in the thalamus may therefore be involved in both the sedative effects of alcohol and the development of alcoholism. Investigating the effects of alcohol on both synaptic and extrasynaptic GABAA-Rs in the thalamus should help us to understand the mechanisms underlying the interaction between alcohol and sleep.

The cancer chemotherapy drug etoposide (VP-16) induces proinflammatory cytokine production and sickness behavior-like symptoms in a mouse model of cancer chemotherapy-related symptoms.

Cancer chemotherapy-related symptoms such as fatigue, malaise, loss of interest in social activities, difficulty concentrating, and changes in sleep patterns can lead to treatment delays, dose reductions, or termination and have a profound effect on the physical, psychosocial, and economic aspects of quality of life. Clinicians have long suspected that these symptoms are similar to those associated with "sickness behavior," which is triggered by the production of the inflammatory cytokines IL-1beta, TNF-alpha, and IL-6 by macrophages and other cells of the innate immune system in response to immune challenge. The p38 mitogen-activated protein kinase (p38 MAPK) plays a central role in the production of these cytokines and consequently the induction of sickness behavior. Several cancer chemotherapy drugs have been shown to activate p38 MAPK, but whether these drugs can also induce the production of inflammatory cytokines to cause sickness behavior is unknown. The aim of this study was to determine whether the cancer chemotherapy drug etoposide (VP-16), which is known to activate p38 MAPK, could induce inflammatory cytokine production by murine macrophages and sickness-like behaviors when injected into mice. VP-16 activated p38 MAPK and induced IL-6 production in murine macrophages in a p38 MAPK- dependent manner. VP-16 administration rapidly increased serum levels of IL-6 in healthy mice and induced sickness-like behaviors as evidenced by a decrease in food intake, body weight, hemoglobin level, and voluntary wheel-running activity. These findings support the idea that the induction of IL-1beta, TNF-alpha, and IL-6 by cancer chemotherapy drugs underlies the fatigue and associated symptoms experienced by people undergoing cancer chemotherapy.

The effect of transdermal nicotine patches on sleep and dreams.

This study was undertaken to determine the effect of 24-h transdermal nicotine patches on sleep and dream mentation in 15 smokers aged 20 to 33. Utilising a repeated measures design, it was found that more time awake and more ASDA micro-arousals occurred while wearing the nicotine patch compared to placebo. Also, the percentage of REM sleep decreased, but REM latency and the proportion of time spent in NREM sleep stages did not change significantly. Dream reports containing visual imagery, visual imagery ratings and the number of visualizable nouns were significantly greater from REM compared to Stage 2 awakenings, regardless of patch condition. However, a general interaction effect was observed. Stage 2 dream variables remained equivalent across nicotine and placebo conditions. Within REM sleep, more dream reports containing visual imagery occurred while wearing the nicotine patch, and these were rated as more vivid. The greater frequency of visual imagery reports and higher imagery ratings specifically from REM sleep suggests that previously reported dreaming side effects from 24-h nicotine patches may be specific to REM sleep. Combined with previous animal studies showing that transdermally delivered nicotine blocks PGO activity in REM sleep, the current results do no appear consistent with PGO-based hypotheses of dreaming, such as the Activation-Synthesis (AS) or Activation, Input and Modulation (AIM) models.

Prenatal ethanol exposure alters the expression of period genes governing the circadian function of beta-endorphin neurons in the hypothalamus.

Sleep-wake disturbances and stress hyper-responsiveness have been observed in human neonates, children and adolescents who were exposed to alcohol during the prenatal period. Using the laboratory rat as an animal model, we investigated whether fetal ethanol exposure during gestational days 10-21 affects the circadian function of the stress-axis regulatory beta-endorphin neurons in the hypothalamus. Fetal ethanol-exposed rats showed abnormality in the circadian expression of proopiomelanocortin (POMC) mRNA encoding the peptide beta-endorphin in the arcuate nucleus of the hypothalamus during the adult period. These rats also showed altered circadian expression of the clock governing Period genes rPer1, rPer2 and rPer3, in the arcuate nucleus, and rPer1 and rPer 2 mRNA levels in the suprachiasmatic nucleus. Laser captured microdissection analysis identified constitutive expression of rPer1, rPer2 and rPer3 genes in beta-endorphin-containing neurons. These data suggest for the first time that fetal exposure to ethanol significantly alters the clock mechanisms governing the circadian function of beta-endorphin neurons.

Chronic ethanol drinking reduces native T-type calcium current in the thalamus of nonhuman primates.

BACKGROUND: Chronic ethanol use is known to disrupt normal sleep rhythms, but the cellular basis for this disruption is unknown. An important contributor to normal sleep patterns is a low-threshold calcium current mediated by T-type calcium channels. The T-type calcium current underlies burst responses in thalamic nuclei that are important to spindle propagation, and we recently observed that this current is sensitive to acute low doses of ethanol. METHODS: We used a combination of current clamp and voltage clamp recordings in an in vitro brain slice preparation of the dorsal lateral geniculate nucleus (LGN) of macaque monkeys that have chronically self-administered ethanol to determine whether chronic ethanol exposure may affect T-type currents. RESULTS: Current clamp recordings from the LGN of ethanol naive macaques showed characteristic burst responses. However, recordings from the LGN in macaques that self-administered ethanol revealed a significant attenuation of bursts across a range of voltages (n=5). Voltage clamp recordings from control LGN neurons (n=16) and neurons (n=29) from brain slices from chronically drinking macaques showed no significant differences (P>0.05) in T-type current kinetics or in the membrane resistance of the thalamic cells between the two cohorts. However, mean T-type current amplitude measured in the chronically drinking animals was reduced by 31% (P<0.01). CONCLUSIONS: We conclude that chronic ethanol self-administration reduces calcium currents in thalamic relay cells without altering underlying current kinetics, which may provide a mechanistic framework for the well-documented disruptions in sleep/wake behavior in subjects with chronic ethanol exposure.