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Peripheral hypoxia in patients with restless legs syndrome
Abstracts / Sleep Medicine 14S (2013) e18–e92
Conclusion: This study indicates that for patients with both diagnoses, treatment with cognitive behavior therapy (CBT) for insomnia may overall be more effective than CBT for depression. Ideally, efforts to treat both conditions should be made. Acknowledgements: This project was funded by the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet, SöderströmKönigska Foundation, KI funds and AFA Sickness Insurance Research Fund. http://dx.doi.org/10.1016/j.sleep.2013.11.054
Impact of comorbidity on insomnia treatment response following cognitive-behavior therapy, behavior therapy, and cognitive therapy L. Bélanger 1, A. Harvey 2, É. Fortier-Brochu 1, S. Beaulieu-Bonneau 1, P. Eidelman 2, L. Talbot 2 1 Université Laval, Centre Hospitalier Universitaire de Québec, Canada 2 University of California at Berkeley, University of California at Berkeley, United States
Introduction: There is a strong evidence-base on the efficacy of cognitive behavior therapy (CBT) for insomnia. Despite high comorbidity rates between insomnia and some anxiety and mood disorders, much less is known about impact of comorbidity on insomnia treatment response. The aim of the present study was to examine whether comorbid anxiety or mood disorders modulate response to insomnia treatment. As the data were derived from a larger study evaluating the unique contribution of behavior therapy (BT) and cognitive therapy (CT) relative to full CBT, we also examined modulating effects of comorbidity within each single treatment condition. Materials and methods: Participants were 188 adults (117 women; M age = 47.4 years, SD = 12.6) meeting DSM-IV-TR diagnostic criteria for chronic insomnia (M duration: 14.5 years, SD: 12.8). Forty-five participants (23.9%) also met criteria for an anxiety or mood disorder (major depression, dysthymia, GAD, Panic Disorder). Participants were randomized to one of three treatment groups, BT (n = 63), CT (n = 65), CBT (n = 60), stratified according to gender and presence of comorbidity. Treatment consisted of eight, weekly, individual sessions delivered by registered psychologists. Outcome measures were insomnia severity, measured by the Insomnia Severity Index (ISI) and usual sleep parameters derived from daily sleep diaries, and proportion of treatment responders (decrease of ISI score P 8) and remissions (ISI score < 8) . The BDI–II and STAI were also used to monitor depression and anxiety levels. Results: In the CBT condition, proportions of treatment responders or remissions were not significantly different between subgroups of individuals with and without comorbidity, and there were very few significant group differences on sleep parameters. Proportion of treatment responders was significantly lower in the comorbidity groups in both BT (81.6% vs 34.4%; p = 0.007) and CT (57.6% vs 23.6%; p = 0.02) conditions, but remission rates were not significantly different, nor were mean pre-post ISI change scores. The comorbidity group’s pre- post change scores on the STAI ( 9.2 vs 2.5; p = .01) and BDI ( 10.6 vs 3.9; p < 0.001) were significantly greater relative to insomnia group without comorbidity group in the CBT condition but not in the other conditions. Conclusion: There is a widespread assumption that psychiatric disorders comorbid to insomnia need to be addressed in order for sleep to improve. The present data suggest otherwise with respect to full CBT, as the presence of comorbid anxiety or unipolar depressive disorders do not appear to negatively impact treatment response. These
e39
results may have important clinical implications as they suggest that comorbidity does not represent a contraindication to insomnia treatment. These results need to be replicated with larger comorbidity samples. Acknowledgements: This project was supported by National Institute of Mental Health Grant RO1MH079188. http://dx.doi.org/10.1016/j.sleep.2013.11.055
Insomnia treatment in the third trimester of pregnancy prevents postpartum depression: a randomized clinical trial M. Tahmasian 1, H. Khazaie 2, M. Ghadami 2, D. Knight 3, F. Emamian 2 1 Sleep Research Center, Department of Psychiatry, Kermanshah University of Medical Sciences(KUMS), Iran 2 Sleep Research Center, Department of Psychiatry, Farabi Hospital, Kermanshah University of Medical Sciences(KUMS), Iran 3 Department of Psychology, University of Alabama at Birmingham, Birmingham, United Kingdom
Introduction: Mental health is an important medical issue in perinatal care, and there is increasing evidence that insomnia during pregnancy is associated with postpartum depression (PPD). Therefore, the present study evaluated the effect of insomnia treatment during the third trimester of pregnancy on PPD symptoms. Materials and methods: Fifty-three pregnant women with insomnia were randomly assigned to trazodone, diphenhydramine, or placebo treatment. Sleep quality was measured by actigraphy at baseline, and after 2 and 6 weeks of treatment. In addition, depression was assessed 2 and 6 weeks after delivery. Results: Trazodone and diphenhydramine improved sleep quality compared to placebo after 6 weeks of treatment. Further, depressive symptoms were reduced 2 and 6 weeks after delivery in trazodone and diphenhydramine groups compared to placebo. No differences in depressive symptoms were observed between the trazodone and diphenhydramine groups. Conclusion: These findings indicate that insomnia treatment with trazodone or diphenhydramine during the third trimester of pregnancy may prevent PPD. Acknowledgements: This study was supported by a grant from Department of Research, Kermanshah University of Medical Sciences (Research No. 86014). We want to thank Ambulatory Monitoring, Inc. (Ardsley, New York) for their technical assistance and lending us actigraphy equipment. http://dx.doi.org/10.1016/j.sleep.2013.11.056
Peripheral hypoxia in patients with restless legs syndrome A. Salminen 1, O. Polo 2 1 University of Tampere, School of Medicine, University of Tampere, Finland 2 Tampere University Hospital, Department of Respiratory Medicine, Finland Introduction: Previous studies suggest that restless legs syndrome (RLS) may be associated with hypoxia in the skeletal muscles: biopsies have shown VEGF upregulation (Wåhlin-Larsson 2009) and structural analysis of the muscle revealed high capillary tortuosity (Larsson 2007). In this study we measured oxygen and carbon dioxide partial pressure (pO2 and pCO2) in the legs of RLS patients and controls in order to evaluate the peripheral hypoxia suggested by these studies more directly.
e40
Abstracts / Sleep Medicine 14S (2013) e18–e92
Materials and methods: A total of 18 subjects (9 patients and 9 age and sex-matched controls) were included in the study. The tissue pO2 and pCO2 were estimated by transcutaneous measurements on the instep of the foot and on the chest. The measurements were performed in the evening, during two repeated suggested immobilization tests (SIT), two and four hours before bedtime. RLS patients went through the measurements once without medication and a second time with dopaminergic therapy. At the same time, arterial oxygen saturation (SaO2) was measured from the toe. Results: The mean tissue pO2 during SIT was lower in the legs of RLS patients than controls (5.1 kPa vs. 7.4 kPa, p < 0.05). The oxygen gradient from chest to foot (=pO2(chest)-pO2(foot)) was higher in RLS compared to controls (3.5 kPa vs. 1.5 kPa, p < 0.05). The oxygen gradient showed a strong positive correlation with IRLSSG severity score (Pearson’s r = 0.570). Dopaminergic therapy resolved the hypoxia, raising the pO2 of the legs almost to the level of the control patients (pO2 = 6.4 kPa, p < 0.05). There was no significant difference in SaO2 or pCO2 measures. Conclusion: Our results confirm that there is a significant peripheral hypoxia in the legs of RLS patients during the symptomatic period. Control subjects showed normal oxygen levels. The strong positive correlation with RLS severity suggests that the leg hypoxia could be a major factor in RLS pathophysiology. The finding that dopaminergic therapy abolishes both the symptoms and the hypoxia may suggest that the site of action of dopamine in RLS is in the periphery. Acknowledgement: The study was supported by Tuberculosis Foundation of Tampere, Finland. http://dx.doi.org/10.1016/j.sleep.2013.11.057
PTPRD expression regulates sleep consolidation in Drosophila A. Freeman 1, D. Rye 1, S. Sanyal 2 1 Emory University, Department of Neurology, United States 2 Biogen Idec, United States
Introduction: Restless legs syndrome/Willis-Ekbom Disease (RLS/ WED) is a common sleep disorder, yet its underlying pathophysiology is poorly understood. Genome-wide association studies (GWAS) point to allelic variants in multiple genes that confer susceptibility to RLS/WED. They offer potential insights into molecular pathways that govern expressivity of symptoms and signs. We used Drosophila melanogaster to explore sleep related physiology of two genes harboring at-risk alleles for RLS which also have highly conserved fly homologs, BTBD9 and PTPRD. Here, we complement our recent report of RLS phenotypes in BTBD9 mutants by exploring whether similar phenotypes exist in PTPRD mutants and probe whether sleep phenotypes are mimicked by dual mutants (i.e., suggesting a common molecular pathway) or are more severely disrupted (i.e., consistent with parallel pathways). Materials and methods: Sleep phenotypes resulting from mutations in the fly homolog of PTPRD (dLar) were assayed with the Drosophila Activity Monitor. Flies transgenic for either mutated or wild-type dLar protein allowed for cell-specific manipulation of expression levels. The impact of combined dLar and BTBD9 mutations on sleep architecture was also assessed. Results: Disruption of dLar/PTPRD expression in flies yielded viable, hyperlocomotive animals. dLar mutants exhibit sleep fragmentation and increased wake after sleep onset similar to that observed in BTBD9 mutant flies, the latter of which bears close resemblance to human RLS. The magnitude of fragmentation, as measured by sleep bout number and average sleep bout length, was not further increased by introduction of BTBD9 mutations into
the dLar mutant background. Neuron specific expression of dLar constructs, using the GAL4-UAS system, yielded disrupted sleep consolidation similar to whole animal dLar mutants. Conclusion: These results further validate GWAS as a hypothesis independent means to delineate the molecular pathophysiology underlying RLS/WED. While the role of PTPRD in neuronal development and plasticity has been studied previously in flies, this is the first exploration of its function in the context of sleep and, more specifically, RLS/WED. Our results suggest neuronal PTPRD expression regulates sleep architecture and most likely operates in a molecular pathway that also includes BTBD9. Ongoing efforts to delineate the mechanistic basis of sleep regulation by PTPRD and BTBD9 are underway. Acknowledgements: Supported by RLS Foundation, Sleep Research Society, and Emory Neuroscience Initiative grants to S.S. http://dx.doi.org/10.1016/j.sleep.2013.11.058
Activity and sleep in a mouse model of Parkinson disease I. Zavalko 1, Y. Ukraintseva 2, A. Manolov 3, V. Dolgikh 4, V. Dorokhov 3, V. Kovalzon 4 1 Institute for Bio-Medical Problems, RAS, Russia 2 Institute of Higher Nervous Activity/Neurophysiology, RAS, Russia 3 Higher Nervous Activity/Neurophysiology, RAS, Russia 4 Severtsov Institute Ecology/Evolution, RAS, Russia
Introduction: The search for early markers of Parkinson’s disease (PD) is one of the most important problems in the struggle against neurodegenerative illnesses. It is well known that large set of sleep-wake disorders occur with PD, including RBD, daytime sleepiness, night sleep disturbance etc. The nature of these is generally unknown. Not infrequently such disorders appear several years (up to 20 years) before motor symptoms of PD. Recently, a new murine model of early stages of PD has been developed [Ugrumov et al., Neuroscience 181 (2011) 175–188]. In this model, two successive subcutaneous injections in C57 black mice (with 2-h interval) of 12 mg/kg MPTP (specific neurotoxin of dopamine neurons) serve to imitate two weeks later pre-clinical PD, and four injections early clinical forms of PD. Materials and methods: A group of mice with preliminary implanted (under general anesthesia) electrodes for cortical EEG and nuchal EMG after a period of postoperative rest and adaptation to recording conditions was subjected to continuous 24-h video and digital polysomnographic recording in individual experimental chambers with 12/12 light/dark schedule, constant temperature (24–260C) and food and water ad lib. After the baseline recording of video-tracking activity and sleep-wake EEG, mice were injected with 24 or 48 mg/kg b.w. of MPTP. Control group was injected with a saline. The recordings were continued for 2 more weeks. Results: A significant increase in activity and decrease in slow wave sleep (SWS) percentage during the dark period ( 25%) as compared to baseline and control recording (100%) was found. The effect was seen just at the 7th day following MPTP administration and became significant by the 14th day. The effect was more pronounced after 48 mg/kg injection than after 24. There was no change in paradoxical sleep (PS). Also, there were no changes either in SWS or PS during the light period. The reason for this increasing activity and diminished SWS level during the dark period in MPTP-treated mice is under study now. Conclusion: The reason for this increasing activity and diminished SWS level during the dark period in MPTP-treated mice is under study now.
Conclusion: This study indicates that for patients with both diagnoses, treatment with cognitive behavior therapy (CBT) for insomnia may overall be more effective than CBT for depression. Ideally, efforts to treat both conditions should be made. Acknowledgements: This project was funded by the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet, SöderströmKönigska Foundation, KI funds and AFA Sickness Insurance Research Fund. http://dx.doi.org/10.1016/j.sleep.2013.11.054
Impact of comorbidity on insomnia treatment response following cognitive-behavior therapy, behavior therapy, and cognitive therapy L. Bélanger 1, A. Harvey 2, É. Fortier-Brochu 1, S. Beaulieu-Bonneau 1, P. Eidelman 2, L. Talbot 2 1 Université Laval, Centre Hospitalier Universitaire de Québec, Canada 2 University of California at Berkeley, University of California at Berkeley, United States
Introduction: There is a strong evidence-base on the efficacy of cognitive behavior therapy (CBT) for insomnia. Despite high comorbidity rates between insomnia and some anxiety and mood disorders, much less is known about impact of comorbidity on insomnia treatment response. The aim of the present study was to examine whether comorbid anxiety or mood disorders modulate response to insomnia treatment. As the data were derived from a larger study evaluating the unique contribution of behavior therapy (BT) and cognitive therapy (CT) relative to full CBT, we also examined modulating effects of comorbidity within each single treatment condition. Materials and methods: Participants were 188 adults (117 women; M age = 47.4 years, SD = 12.6) meeting DSM-IV-TR diagnostic criteria for chronic insomnia (M duration: 14.5 years, SD: 12.8). Forty-five participants (23.9%) also met criteria for an anxiety or mood disorder (major depression, dysthymia, GAD, Panic Disorder). Participants were randomized to one of three treatment groups, BT (n = 63), CT (n = 65), CBT (n = 60), stratified according to gender and presence of comorbidity. Treatment consisted of eight, weekly, individual sessions delivered by registered psychologists. Outcome measures were insomnia severity, measured by the Insomnia Severity Index (ISI) and usual sleep parameters derived from daily sleep diaries, and proportion of treatment responders (decrease of ISI score P 8) and remissions (ISI score < 8) . The BDI–II and STAI were also used to monitor depression and anxiety levels. Results: In the CBT condition, proportions of treatment responders or remissions were not significantly different between subgroups of individuals with and without comorbidity, and there were very few significant group differences on sleep parameters. Proportion of treatment responders was significantly lower in the comorbidity groups in both BT (81.6% vs 34.4%; p = 0.007) and CT (57.6% vs 23.6%; p = 0.02) conditions, but remission rates were not significantly different, nor were mean pre-post ISI change scores. The comorbidity group’s pre- post change scores on the STAI ( 9.2 vs 2.5; p = .01) and BDI ( 10.6 vs 3.9; p < 0.001) were significantly greater relative to insomnia group without comorbidity group in the CBT condition but not in the other conditions. Conclusion: There is a widespread assumption that psychiatric disorders comorbid to insomnia need to be addressed in order for sleep to improve. The present data suggest otherwise with respect to full CBT, as the presence of comorbid anxiety or unipolar depressive disorders do not appear to negatively impact treatment response. These
e39
results may have important clinical implications as they suggest that comorbidity does not represent a contraindication to insomnia treatment. These results need to be replicated with larger comorbidity samples. Acknowledgements: This project was supported by National Institute of Mental Health Grant RO1MH079188. http://dx.doi.org/10.1016/j.sleep.2013.11.055
Insomnia treatment in the third trimester of pregnancy prevents postpartum depression: a randomized clinical trial M. Tahmasian 1, H. Khazaie 2, M. Ghadami 2, D. Knight 3, F. Emamian 2 1 Sleep Research Center, Department of Psychiatry, Kermanshah University of Medical Sciences(KUMS), Iran 2 Sleep Research Center, Department of Psychiatry, Farabi Hospital, Kermanshah University of Medical Sciences(KUMS), Iran 3 Department of Psychology, University of Alabama at Birmingham, Birmingham, United Kingdom
Introduction: Mental health is an important medical issue in perinatal care, and there is increasing evidence that insomnia during pregnancy is associated with postpartum depression (PPD). Therefore, the present study evaluated the effect of insomnia treatment during the third trimester of pregnancy on PPD symptoms. Materials and methods: Fifty-three pregnant women with insomnia were randomly assigned to trazodone, diphenhydramine, or placebo treatment. Sleep quality was measured by actigraphy at baseline, and after 2 and 6 weeks of treatment. In addition, depression was assessed 2 and 6 weeks after delivery. Results: Trazodone and diphenhydramine improved sleep quality compared to placebo after 6 weeks of treatment. Further, depressive symptoms were reduced 2 and 6 weeks after delivery in trazodone and diphenhydramine groups compared to placebo. No differences in depressive symptoms were observed between the trazodone and diphenhydramine groups. Conclusion: These findings indicate that insomnia treatment with trazodone or diphenhydramine during the third trimester of pregnancy may prevent PPD. Acknowledgements: This study was supported by a grant from Department of Research, Kermanshah University of Medical Sciences (Research No. 86014). We want to thank Ambulatory Monitoring, Inc. (Ardsley, New York) for their technical assistance and lending us actigraphy equipment. http://dx.doi.org/10.1016/j.sleep.2013.11.056
Peripheral hypoxia in patients with restless legs syndrome A. Salminen 1, O. Polo 2 1 University of Tampere, School of Medicine, University of Tampere, Finland 2 Tampere University Hospital, Department of Respiratory Medicine, Finland Introduction: Previous studies suggest that restless legs syndrome (RLS) may be associated with hypoxia in the skeletal muscles: biopsies have shown VEGF upregulation (Wåhlin-Larsson 2009) and structural analysis of the muscle revealed high capillary tortuosity (Larsson 2007). In this study we measured oxygen and carbon dioxide partial pressure (pO2 and pCO2) in the legs of RLS patients and controls in order to evaluate the peripheral hypoxia suggested by these studies more directly.
e40
Abstracts / Sleep Medicine 14S (2013) e18–e92
Materials and methods: A total of 18 subjects (9 patients and 9 age and sex-matched controls) were included in the study. The tissue pO2 and pCO2 were estimated by transcutaneous measurements on the instep of the foot and on the chest. The measurements were performed in the evening, during two repeated suggested immobilization tests (SIT), two and four hours before bedtime. RLS patients went through the measurements once without medication and a second time with dopaminergic therapy. At the same time, arterial oxygen saturation (SaO2) was measured from the toe. Results: The mean tissue pO2 during SIT was lower in the legs of RLS patients than controls (5.1 kPa vs. 7.4 kPa, p < 0.05). The oxygen gradient from chest to foot (=pO2(chest)-pO2(foot)) was higher in RLS compared to controls (3.5 kPa vs. 1.5 kPa, p < 0.05). The oxygen gradient showed a strong positive correlation with IRLSSG severity score (Pearson’s r = 0.570). Dopaminergic therapy resolved the hypoxia, raising the pO2 of the legs almost to the level of the control patients (pO2 = 6.4 kPa, p < 0.05). There was no significant difference in SaO2 or pCO2 measures. Conclusion: Our results confirm that there is a significant peripheral hypoxia in the legs of RLS patients during the symptomatic period. Control subjects showed normal oxygen levels. The strong positive correlation with RLS severity suggests that the leg hypoxia could be a major factor in RLS pathophysiology. The finding that dopaminergic therapy abolishes both the symptoms and the hypoxia may suggest that the site of action of dopamine in RLS is in the periphery. Acknowledgement: The study was supported by Tuberculosis Foundation of Tampere, Finland. http://dx.doi.org/10.1016/j.sleep.2013.11.057
PTPRD expression regulates sleep consolidation in Drosophila A. Freeman 1, D. Rye 1, S. Sanyal 2 1 Emory University, Department of Neurology, United States 2 Biogen Idec, United States
Introduction: Restless legs syndrome/Willis-Ekbom Disease (RLS/ WED) is a common sleep disorder, yet its underlying pathophysiology is poorly understood. Genome-wide association studies (GWAS) point to allelic variants in multiple genes that confer susceptibility to RLS/WED. They offer potential insights into molecular pathways that govern expressivity of symptoms and signs. We used Drosophila melanogaster to explore sleep related physiology of two genes harboring at-risk alleles for RLS which also have highly conserved fly homologs, BTBD9 and PTPRD. Here, we complement our recent report of RLS phenotypes in BTBD9 mutants by exploring whether similar phenotypes exist in PTPRD mutants and probe whether sleep phenotypes are mimicked by dual mutants (i.e., suggesting a common molecular pathway) or are more severely disrupted (i.e., consistent with parallel pathways). Materials and methods: Sleep phenotypes resulting from mutations in the fly homolog of PTPRD (dLar) were assayed with the Drosophila Activity Monitor. Flies transgenic for either mutated or wild-type dLar protein allowed for cell-specific manipulation of expression levels. The impact of combined dLar and BTBD9 mutations on sleep architecture was also assessed. Results: Disruption of dLar/PTPRD expression in flies yielded viable, hyperlocomotive animals. dLar mutants exhibit sleep fragmentation and increased wake after sleep onset similar to that observed in BTBD9 mutant flies, the latter of which bears close resemblance to human RLS. The magnitude of fragmentation, as measured by sleep bout number and average sleep bout length, was not further increased by introduction of BTBD9 mutations into
the dLar mutant background. Neuron specific expression of dLar constructs, using the GAL4-UAS system, yielded disrupted sleep consolidation similar to whole animal dLar mutants. Conclusion: These results further validate GWAS as a hypothesis independent means to delineate the molecular pathophysiology underlying RLS/WED. While the role of PTPRD in neuronal development and plasticity has been studied previously in flies, this is the first exploration of its function in the context of sleep and, more specifically, RLS/WED. Our results suggest neuronal PTPRD expression regulates sleep architecture and most likely operates in a molecular pathway that also includes BTBD9. Ongoing efforts to delineate the mechanistic basis of sleep regulation by PTPRD and BTBD9 are underway. Acknowledgements: Supported by RLS Foundation, Sleep Research Society, and Emory Neuroscience Initiative grants to S.S. http://dx.doi.org/10.1016/j.sleep.2013.11.058
Activity and sleep in a mouse model of Parkinson disease I. Zavalko 1, Y. Ukraintseva 2, A. Manolov 3, V. Dolgikh 4, V. Dorokhov 3, V. Kovalzon 4 1 Institute for Bio-Medical Problems, RAS, Russia 2 Institute of Higher Nervous Activity/Neurophysiology, RAS, Russia 3 Higher Nervous Activity/Neurophysiology, RAS, Russia 4 Severtsov Institute Ecology/Evolution, RAS, Russia
Introduction: The search for early markers of Parkinson’s disease (PD) is one of the most important problems in the struggle against neurodegenerative illnesses. It is well known that large set of sleep-wake disorders occur with PD, including RBD, daytime sleepiness, night sleep disturbance etc. The nature of these is generally unknown. Not infrequently such disorders appear several years (up to 20 years) before motor symptoms of PD. Recently, a new murine model of early stages of PD has been developed [Ugrumov et al., Neuroscience 181 (2011) 175–188]. In this model, two successive subcutaneous injections in C57 black mice (with 2-h interval) of 12 mg/kg MPTP (specific neurotoxin of dopamine neurons) serve to imitate two weeks later pre-clinical PD, and four injections early clinical forms of PD. Materials and methods: A group of mice with preliminary implanted (under general anesthesia) electrodes for cortical EEG and nuchal EMG after a period of postoperative rest and adaptation to recording conditions was subjected to continuous 24-h video and digital polysomnographic recording in individual experimental chambers with 12/12 light/dark schedule, constant temperature (24–260C) and food and water ad lib. After the baseline recording of video-tracking activity and sleep-wake EEG, mice were injected with 24 or 48 mg/kg b.w. of MPTP. Control group was injected with a saline. The recordings were continued for 2 more weeks. Results: A significant increase in activity and decrease in slow wave sleep (SWS) percentage during the dark period ( 25%) as compared to baseline and control recording (100%) was found. The effect was seen just at the 7th day following MPTP administration and became significant by the 14th day. The effect was more pronounced after 48 mg/kg injection than after 24. There was no change in paradoxical sleep (PS). Also, there were no changes either in SWS or PS during the light period. The reason for this increasing activity and diminished SWS level during the dark period in MPTP-treated mice is under study now. Conclusion: The reason for this increasing activity and diminished SWS level during the dark period in MPTP-treated mice is under study now.