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. . // . .: , 1983. 6.
. 62-71.
Basheer R., Strecker R. ., Thakkar . ., McCarley R. W. Adenosine and sleepwake regulation// Progress in Neurobiology. 2004. V. 73. P. 379-396.
Bassetti C. L., Bischof ., Valko P. Dreaming: a neurological view // Psycho
analysis and Neuroscience / Ed. M. Mancia. Springer: Milan, 2006.
P. 351-387.

42

B lanco-C enturion . et al. Adenosine and sleep homeostasis in the basal fore
brain // J. Neurosci. 2006. V. 26. No. 31. P. 8092-8100.
B orbely A. A. et al. (eds.) The regulation o f sleep. Human Frontier Science
Program: Strasbourg, 2000.
D ang- Vu T. 7'., D esseilles A/., P etit D. et al. Neuroimaging in sleep medicine //
Sleep Medicine. 2007. V. 8. P. 349-372.
D atta S ., M acLean R. R. Neurobiological m echanism s for the regulation o f
m am m alian sleep-w ake behavior: Reinterpretation o f historical evidence
and inclusion o f contemporary cellular and m olecular evidence // Neuro
science and Biobehavioral Reviews. 2007. V. 31. P. 775-824.
D o m h o ff G. W. Foundations for a new neurocognitive theory o f dream s //
Front. Neurosci. 2009. V. 3. No. 3. P. 439.
E spana R .A ., ScammeU . E. Sleep neurobiology for the clinician // Sleep.
2004. V. 27. No. 4. P. 811-820.
F ort P ., B assetti C. L., Luppi P.-H. Alternating vigilance states: new insights
regarding neuronal networks and m echanism s // European Journal o f N eu
roscience. 2009. V. 29. P. 1741-1753.
Gottesmann C. Brain inhibitory mechanisms involved in basic and higher inte
grated sleep processes // Brain Research Reviews. 2004. V. 45. P. 2 3 0 - 249.
H uang Z.-L., Grade ., H ayaishi O. Prostaglandins and adenosine in the re g u
lation o f sleep and wakefulness // Current Opinion in Pharmacology. 2007.
V. 7. P. 33-38.
Jo n es . E. Activity, m odulation and role o f basal forebrain cholinergic neu
rons innervating the cerebral cortex // Prog. Brain Res. 2004. V. 145.
P . 157-169.
Jo n es . E. Arousal systems // Frontiers in Bioscience. 2003. V. 8. Suppl.
P. 4 38 -45 1.
Jo n es . E. Basic m echanism s o f sleep-wrake states // Principles and Practice
o f Sleep Medicine, 4th ed. / Kryger . H., Roth ., Dem ent W. C., eds.
Elsevier: Am sterdam, 2005a. P. 136-153.
Jo n es . E. From waking to sleeping: neuronal and chemical substrates //
Trends in Pharm acological Sciences. 2005b. V. 26. No. 11. P. 578-586.
Jo n es . E. Modulation o f cortical activation and behavioral arousal by ch o
linergic and orexinergic s y s te m s / / Ann. N.Y. Acad. Sci. 2008. V. 1129.
P. 2 6-3 4.
Landolt H.-P. Sleep homeostasis: A role for adenosine in hum ans? // Bioche
mical Phannacology. 2008. V. 75. P. 2070-2079.
L u J ., Sherman D ., D ev o r ., S a p er . B. A putative flip-flop switch for con
trol o f REM sleep. Nature. 2006. V. 441. No. 7093. P. 589-594.
M cC arley R. W. Neurobiology o f REM and NREM sleep // Sleep Medicine.
2007. V. 8. P. 302-330.

43

M ignol . W hy we sleep: the temporal organization o f recovery // PLoS Bio


logy. 2008. V. 6. No. 4. P. 661-669.
M o r a ir ty S ., R a in n ie D ., M e C ar ley R ., G reen e R. D isin h ib itio n o f v e n tro
lateral p reo p tic area sleep -activ e n e u ro n s b y ad e n o sin e : a new m e c h a
nism for sleep p ro m o tio n // N eu ro sc ie n c e . 2004. V. 123. No. 2.
P. 4 5 1 - 4 5 7 .
Pigarev I. N. Neurons o f visual cortex respond to visceral stimulation during
slow wave sleep // Neuroscience. 1994. V. 62. No. 4. P. 1237-1243.
Rechtschaffen A ., Siegel J. M. Sleep and dreaming // In: Kandel E. R. et al.,
Eds. Principles o f Neuroscience, 4th Ed. McGraw-Hill: N.Y., 2000.
P. 936-947.
R offw arg H. R. Participation o f REM sleep in the development o f the brain:
starting hypothesis, unfolding data, current perspective // SRS Bulletin.
2009. V. 15. No. 2. P. 6-7.
Rosenwasser A. M. Functional neuroanatomy o f sleep and circadian rhythms //
Brain Res. Rev. 2009. V. 61. P. 281-306.
Sakai K., Crochet S. A neural mechanism o f sleep and wakefulness // Sleep
and Biological Rhythms. 2003. V. 1. P. 2 9-42 .
Sakai K., Crochet S. Pontine structures and m echanisms involved in the g e
neration o f paradoxical (REM ) sleep // Archives Italiennes de Biologie.
2001. V. 139. P. 93-107.
Siegel J. M. REM sleep // Principles and Practice o f Sleep Medicine, 4th ed. /
Kryger . H., Roth ., Dem ent W.C., eds. Elsevier: Am sterdam, 2005.
P. 120-135.
So Im s M. Freudian dream s today //F ro n t. Neurosci. 2009. V. 3. No. 3. P. 453.
Staunton H. M am m alian sleep // Naturwissenschaften. 2005. V. 92. P. 2 0 3 2 20 .
Stenberg D. Neuroanatomy and neurochem istry o f sleep // Cell. Mol. Life Sci.
2007. V. 64. No. 10. P. 1187-1204.
Steriade M. Brain electrical activity and sensory processing during waking
and sleep states // Principles and Practice o f Sleep Medicine, 4th ed. /
K ryger . H., Roth ., Dement W. C., eds. Elsevier:Am sterdam, 2005.
P. 101-119.
Steriade M. Grouping o f brain rhythms in corticothalamic systems // N euro
science. 2006. V. 137. P. 1087-1106.
Z isapel N. Sleep and sleep disturbances: biological basis and clinical impli
c a tio n s // Cell. Mol. Life Sci. 2007. V. 64. No. 10. P. 1174-1186.


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A dam antidis ., de Lecea L. Physiological arousal: a role for hypothalamic
s y s te m s // Cell. Mol. Life Sci. 2008. V. 65. P. 1475-1488.
Baum ann C. R ., B assetti C. L. Hypocretins (orexins): clinical impact o f the
discovery o f a neurotransm itter II Sleep M edicine Reviews. 2005. V. 9.
P. 25 3-268.

67

Ferguson . ., Sam son W. J. The orexin/hypocretin system: a critical regu


lator o f neuroendocrine and autonomic function // Frontiers in N euroendo
crinology. 2003. V. 24. 1. P. 141-150.
John J. et al. Cataplexy-active neurons in the hypothalamus: implications for
the role o f histam ine in sleep and waking behavior //N e u ro n . 2004. V. 42.
5. P. 619-634.
John
Wu M .-F., Siegel J. M. Systemic Administration o f hypocretin-1
reduces cataplexy and normalizes sleep and w aking durations in narco
leptic dogs // Sleep Research Online. 2000. V. 3. No. 1. P. 23-28.
K ild u ff T. S ., Peyron C. The hypocretin/'orexin ligand-receptor system:
implications for sleep and sleep disorders // TINS. 2000. V .2 3 . 8 .
P. 359-365.
K ild u ff T. S. Hypocretin/hypocretin: m aintenance o f wakefiilness and a m ul
tiplicity o f other roles // Sleep Med. Rev. 2005. V. 9. P. 227-230.
Lu

Sherm an D ., D e v o r ., S a p er . B. A pu tative flip-flop sw itch


for control o f REM sleep // N ature. 2006. V. 441. No. 7093. P. 5 8 9 594.

M a tsu k i ., S a k u ra i T. O re x in s and orexin receptors: from m o lecu les


to in teg rativ e p h y sio lo g y // O rp h a n G -p ro te in -c o u p le d re cep to rs
and novel n e u ro p e p tid e s (R esu lts Probl. C ell D iffer. V . 4 6 ) / Eds.
C iv elli O ., Z hou Q .-Y . S p rin g er-V erlag : B erlin, H eid e lb e rg , 2008.
P. 2 7 -5 5 .
M ignot E. Perspectives in narcolepsy and hypocretin (orexin) research // Sleep
Medicine. 2000. V. 1. 1. P. 87-90.
M ignot E. Narcolepsy as a model for brain autoim m une diseases // Frontiers in
neuroscience. 2009. V. 3. No. 3. P. 426-427.
Sakurai T. Physiological reviews: roles o f hypocretin/hypocretin in regulation
o f sleep/wakefulness and energy homeostasis // Sleep Med. Rev. 2005.
V. 9. P. 231-242.
Saper C. B .,S ca m m elI T. E .,L u J. Hypothalam ic regulation o f sleep and circa
dian rhythm s // Nature. 2005. V. 437. P. 1257-1263.
Scam m el . E. An eye-opening perspective on orexin neurons // Current Bio
logy. 2001. V. 11. P. R 769-R 771.
S ieg el J. M . H ypocretin (orexin): R ole in norm al b ehavior and n eu ro
patholog y // A nnual R eview o f P sychology. 2004. V. 55. 2.
P. 125-148.
Siegel J. M , M oore R., Thannickal ., N ienhuiset R. A brief history o fh y p o cretin/orexin and narcolepsy // Neuropsychopharm acology. 2001. V. 25.
S5. P. 14-20.

68
S ieg el J. M. Narcolepsy II Scientific American. 2000. V. 282. P. 76-81.
Torterolo P S a m p o g n a S., M orales F. R., Chase . . M CH-containing
neurons in the hypothalam us o f the cat: Searching for a role in the control
o f sleep and wakefulness // Brain Research. 2006. V. 1119. No. 1.
P. 101-114.
W urtman R .J . Narcolepsy and the hypocretins // Metabolism. Clinical and
Experimental. 2006. V. 55. Suppl 2. P. 36-39.


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Brain. Lipincott, W illiams, and Wilkins, Baltim ore. 2000.

72

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A dam antidis ., de Lecea L. Physiological arousal: a role for hypothalamic
systems // Cell. Mol. Life Sci. 2008. V. 65. P. 1475-1488.
A ton S .J ., H erzog E. D. C om e together, right ... now: synchronization o f
rhythm s in a m am m alian circadian clock // Neuron. 2005. V. 48. No. 4.
P. 531-534.
B e n lo u e if S., Zee P. C. Suprachiasmatic nucleus (SCN) // Encyclopedia o f
the Neurological Sciences. 2003. Elsevier Science (USA). P. 446^447.
F ield M. D. et al. Analysis o f clock proteins in mouse SCN demonstrates phy
logenetic divergence o f the circadian clockw ork and resetting m echa
nism s // Neuron. 2000. V .2 5 . No. 2. P. 4 37 -44 7.
F uller P. M ., G ooley J. .7., S a p er . B. Neurobiology o f the sleep-wake cycle:
sleep architecture, circadian regulation, and regulatory feed b ack // Journal
o f Biological Rhythms. 2006. V. 21. No. 6. P. 4 82-493 .
G illette M. U ., Sabra M.A. Fundam entals o f the Circadian System // SRS Ba
sics o f Sleep Guide / Eds. Am laner C. J., Buxton . M. Sleep Research
Society, Westchester, 1L, 2007. P. 131-140.

87

G uillaum ond F. et al. Differential control o f Bmall circadian transcription by


REV-ERB and ROR nuclear receptors / / J. Biol. Rhythms. 2005. V. 20.
No. 5. P. 391-403.
Lack L. C., Wright H. R. Chronobiology o f sleep in hum ans // Cell. Mol. Life
Sci. 2007. V. 64. No. 10. P. 1205-1215.
Lee C. et al. Posttranslational m echanism s regulate the m am m alian circadian
clock // Cell. 2001. V. 107. No. 7. P. 855-867.
Li Y. et al. DEC 1 negatively regulates the expression o f DEC2 through binding
to the E-box in the proximal prom oter // J. Biol. Chem. 2003. V. 278.
No. 19. P. 16899-16907.
M e ije rJ . H ., S c h a a p W a t a n a h e K., A lh u s . Multiunit activity recordings
in the suprachiasmatic nuclei: in vivo versus in vitro m odels // Brain Res.
1997. V. 753. P. 322-327.
M istlberger R. E. Circadian regulation o f sleep in mammals: Role o f the supra
chiasmatic nucleus // Brain Research Reviews. 2005. V. 49. P. 429-^454.
N itabach M. N. Circadian rhythms: clock coordination// Nature. 2005. V. 438.
No. 7065. P. 173-175.
Panda S. et al. Coordinated transcription o f key pathways in the m ouse by the
circadian clock // Cell. 2002. V. 109. No. 3. P. 307-320.
Ralph M. R ., Lehm an M. N. Transplantation: a new tool in the analysis o f the
m am m alian hypothalam ic circadian pacem aker // Trends Neurosci. 1991.
V. 14. P. 362-366.
Rom ijn H. J. et al. Evidence from confocal fluorescence m icroscopy for
a dense, reciprocal innervation between AVP-, somatostatin-, V1P/PH1-,
GRP-, and V IP/PH I/G RP-im m unoreactive neurons in the rat suprachias
matic nucleus // Eur J Neurosci. 1997. V. 9. P. 2613-2623.
Saper . ., Cano G ., Scam m ell . E. Elomeostatic, circadian, and emotional
regulation o f sleep // The Journal o f Com parative Neurology. 2005. V. 493.
P. 92-98.
Saper . ., L u C h o u . C., Gooley d. The hypothalamic integrator for cir
cadian rhythms // Trends in Neurosciences. 2005a. V. 28. No. 3. P. 152
157.
Saper . B., Scam m ell T. E . , L u J . Hypothalamic regulation o f sleep and circa
dian rhythm s // Nature. 2005b. V. 437. P. 1257-1263.
S ilver R ., L eSauter J. Circadian and homeostatic factors in arousal // Ann.
N. Y. Acad. Sci. 2008. V. 1129. P. 263-274.
Schibler C., Sassone-C orsi P. A w eb o f circadian pacem akers // Cell. 2002.
V. 111. No. 7. P. 919-922.
Szym usiak R., G vilia /., M cG inty D. Hypothalamic control o f sleep // Sleep
Medicine. 2007. V. 8. P. 291-301.

88

Szym usiak R., M cG inty D. Hypothalam ic regulation o f sleep and arousal //


Ann. N. Y. Acad. Sci. 2008. V. 1129. P. 27 5-286.
Taheri S ., M ignot E. The genetics o f sleep disorders // Lancet Neurol. 2002.
V. 1. No. 4. P. 242-250.
Toh K. L. et a\. An hPer2 phosphorylation site mutation in familial advanced
sleep phase syn d ro m e//S cien ce. 2001. V. 291. No. 5506. P. 1040-1043.
Van G elder R. N. Recent insights into m am malian circadian rhythms // Sleep.
2004. V. 27. No. 1. P. 166-171.
W u lffK . et al. Sleep and circadian rhythm disturbances: m ultiple genes and
m ultiple phenotypes // Current Opinion in Genetics & Development. 2009.
V. 19. P. 237-246.
Yam azaki S. et al. Resetting central and peripheral circadian oscillations in
transgenic rats // Science. 2000. V. 288. No. 5466. P. 682-685.
Z ee P. C., M anthena P. The brain s master circadian clock: Implications and
opportunities for therapy o f sleep disorders // Sleep M edicine Reviews.
2006. V. 11. No. 1. P. 59-70.
Z ucconi M . Article reviewed: Familial advanced sleep phase syndrom e //
Sleep Med. 2002. V. 3. No. 2. P. 177-178.


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// :
(. . 1- . .). , 1985.
C. 129-131.
. ., . . :
. .: , 1974.
C ajochen ., K rduchi ., Wurtz-.Justice A. The acute soporific action o f day
time melatonin administration: effects on the EEG during wakefulness and
subjective alertness // J. Biol. Rhythms. 1997. V. 2. No. 6. P. 636-643.
C zeisler C., Turek F. W ., eds. M elatonin, Sleep and Circadian Rhythms: cur
rent progress and controversies // J. Biol. Rhythms. 1997. V. 12. No. 6.
P. 4 8 5 -7 1 4 .
D escam ps A. et al. Influence o f the novel antidepressant and melatonin agonist/serotonin2C receptor antagonist, agomelatine, on the rat sleep-w ake
cycle architecture // Psychopharmacology. 2009. V. 205. P. 93-106.

110

D ijk D .-J., C ajochen . Melatonin and the circadian regulation o f sleep initia
tion, consolidation, structure, and the sleep EEG / / J. Biol. Rhythms. 1997.
V. 2. No. 6. P. 627-635.
F oulkes N. S. et al. Rhythmic transcription: the molecular basis o f circadian
m elatonin synthesis // Trends Neurosci. 1997. V. 20. P. 487-492.
F raschini F., Stankov B. High affinity melatonin receptors in the vertebrate
brain: implications for the control o f the endogenous oscillatory systems //
Chronobiologia. 1994. V .2 1 . P. 89-92.
H ardeland R., B alzer I., P o eggeler B. et al. O n the primary functions o f mela
tonin in evolution m ediation o f photoperiodic signals in a unicell, ph o
tooxidation, and scavenging o f free-radicals / / J. Pineal Res. 1995. V. 18.
No. 2. P. 104-111.
H olm es S. W., Sugden D. Effects o f melatonin on sleep and neurochemistry
in the rat // Br. J. Pharmac. 1982. V. 76. P. 95-101.
H uber R., D eB oer ., Schw ierin B., Tobler I. Effect o f melatonin on sleep and
brain tem perature in the Djungarian hamster and the rat //Physiol. Behav.
1998. V. 65. No. 1. P. 77-82.
Lan .-., H su J .-C ., L in g .-. Influence o f sleep deprivation coupled with
administration o f melatonin on the ultrastructure o f rat pineal gland // Brain
Research. 2001. V. 910. P. 1-11.
L avie P ., L uboshitzky R. Melatonin: possible role in hum an sleep and repro
duction// Sleep and sleep disorders: from m olecule to behavior // Sleep and
sleep disorders: from molecule to behavior/ Eds. Hayaishi O., inoue S.
Tokyo: Academic Press, 1997. P. 20 9-222.
M a illiet P ., G alloux P ., P oisson D. Comparative effects o f m elatonin, zolpidem and diazepam on sleep, body temperature, blood pressure and heart
rate measured by radiotelem etry in Wistar rats // Psychopharmacology.
2001. V. 156. P. 4 17-42 6.
M arczynski T. J., Yamaguchi N., Ling G. M , Grodzinska L. Sleep induced by
the administration o f melatonin (5-methoxyn-acetyltryptamine) to the hypo
thalamus in unrestrained cats//Experientia. 1964. V. 20. No. 8. P. 4 3 5 -4 3 7 .
M endelson W. B. Efficacy o f melatonin as a hypnotic agent / / J. Biol. Rhythms.
1997. V. 12. No. 6. P. 651-656.
M irm iran A/., P evet P. Effects o f melatonin and 5-methoxytryptamine on
sleep-wake patterns in the male rat//.I. Pineal Res. 1986. V. 3. P. 135-141.
N onno R ., C apsoni S ., Lucini V. et al. Distribution and characterization o f the
melatonin receptors in the hypothalam us and pituitary gland o f three do
m estic ungulates // J. Pineal Res. 1995. V. 18. P. 207-216.
P andi-P erum al S. R. et al. Physiological effects o f melatonin: Role o f mela
tonin receptors and signal transduction pathways // Progress in Neuro
biology. 2008. V. 85. P. 335-353.

111

P a n d i-P em m a l S. R. et al. Ramelteon: a Review o f its Therapeutic Potential in


Sleep Disorders // Adv. Ther. 2009. V. 26. No. 6. P. 613-626.
R eppert S. M. M elatonin receptors: m olecular biology o f a new family o f G-protein-coupled re cep to rs/ / J . Biol. Rhythms. 1997. V.12. No. 6. P. 528-531.
Sim onneaux K, R ibelayga C. Generation o f the m elatonin endocrine m essage
in mammals: a review o f the com plex regulation o f m elatonin synthesis by
norepinephrine, peptides, and other pineal transmitters // Pharmacological
Reviews. 2003. V. 55. No. 2. P. 325-395.
Skinner D. C., M alpaux B. High melatonin concentrations in third ventricular
cerebrospinal fluid are not due to G alen vein blood recirculating through
the choroid plexus // Endocrinology. 1999. V. 140. P. 4399-4405.
Sm ale L., C astleberry C., N unez A. A. Fos rhythms in the hypothalam us o f
Rattus and Arvicanthis that exhibit nocturnal and diurnal patterns o f rhythmicity // Brain Research. 2001. V. 899. P. 101-105.
Stankov ., Cozzi B., Lucini V., C apsoni S. et al. Localization and charac
terization o f melatonin binding sites in the brain o f the rabbit // Neurosci.
Lett. 1991. V.133. No. 11. P. 68-72.
Stankov B., C ozzi ., Lucini V. et al. Characterization and mapping o f m ela
tonin receptors in the brain o f three m am m alian species: rabbit, horse and
sheep // Neuroendocrinol. 1991. V. 53. P. 214-221.
Stankov B., M o ller M ., L ucini V., C apsoni S. et al. A carnivore species (Canis
familiaris) expresses circadian melatonin rhythm in the peripheral blood
and melatonin receptors in the brain // Eur. J. Endocrinol. 1994. V. 131.
No. 8. P. 191-200.
S u g d en D. Sedative p o tency and 2 - [ 125l]io d o m elato n in binding affinity
o f m elatonin a n a l o g u e s // P sycho pharm acolo gy. 1995. V. 117. No. 3.
P. 3 6 4 -3 7 0 .
Tan D.-X. et al. Melatonin: a hormone, a tissue factor, an autocoid, a paracoid,
and an antioxidant vitamin // J. Pineal Res. 2003. V. 34. P. 75-78.
Tobler I., D eboer T. Sleep in the Blind Mole Rat Spalax E hrenbergi H Sleep.
2001. V. 24. No. 2. P. 147-154.
Tobler /., Ja g g i ., B orbely A. A. Effects o f melatonin and the melatonin re
ceptor agonist S-20098 on the vigilance states, EEG spectra, and cortical
temperature in the rat // J. Pineal Res. 1994. V. 16. No. 1. P. 2 6 -32.
Wurtman R. ./., L ieberm an H. R. Melatonin secretion as a mediator o f circa
dian variations in sleep and sleepiness // J. Pineal Res. 1985. V. 2.
P. 301-303.
Zhdanova I. V., Friedm an L. M elatonin for treatm ent o f sleep and mood dis
orders // Natural m edications for psychiatric disorders: considering the
alternatives / Eds. M ischoulon D., Rosenbaum J. Lippincot: Williams &
Wilkins, 2002. P. 147-174.

112

Zhdanova I. F., G eiger D. A ., Schw agerl A. L. et al. Melatonin prom otes sleep
in three species o f diurnal nonhum an primates // Physiol. Behav. 2002.
V. 75. P. 523-529.
Zhdanova I. P., Lynch H . W u r t m a n R. J. Melatonin: a sleep-promoting hor
m one // Sleep. 1997. V. 20. No. . P. 899-907.
Zhdanova I. V., W urtman R. J. Efficacy o f melatonin as a sleep-rpomoting
a g e n t// J. Biol. Rhythms. 1997. V. 12. No. 6. P. 644-650.
Zhdanova I. K, W urtman R. J. The pineal horm one melatonin // Endocri
nology: basic and clinical principles / Eds.: C onn P. ., Melmed S. H um a
na Press: Totowa, N .J ., 1998. P. 279-290.
Z isa p el N. Medications for sleep // Frontiers in Neuroscience. 2009. V. 3.
No. 3. P. 434-435.


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118


. / . . . iM. . .: . 1989.
(w w w .sleep.ru).
A cherm ann ., B o rb elyA . A. Mathematical m odels o f sleep regulation // Fron
tiers in Bioscience. 2003. V. 8. P. s683-s693.
B orbely A. A ., A cherm ann P. Sleep hom eostasis and models o f sleep regu
lation // Principles and Practice o f Sleep Medicine, 4 th ed. / Kryger . H.,
Roth ., Dem ent W. C., eds. Elsevier: Am sterdam , 2005. P. 4 05 -4 17.
D ijk D .-J., Franken P. Interaction o f sleep homeostasis and circadian rhythmicity: dependent or independent systems? // Principles and Practice
o f Sleep Medicine, 4 th ed. / Kryger . H., Roth ., Dement W. C., eds.
Elsevier: Am sterdam , 2005. P. 4 18 -43 4.
H uber R., Tononi G ., C irelli C. Exploratory behavior, cortical BDNF expres
sion, and sleep hom eostasis // Sleep. 2006. V. 30. No. 2. P. 129-139.
Silver R., L eSauter J. Circadian and homeostatic factors in arousal II Ann.
N.Y. Acad. Sci. 2008. V. 1129. P. 2 63-274.
Tononi G., Cirelli C. Sleep and synaptic homeostasis: a hypothesis // Brain
Research Bulletin. 2003. V. 62. P. 143-150.

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A ndretic R. el al. Genetics o f sleep // Annu. Rev. Genet. 2008. V. 42. P. 361
388.
C antero J. L. Sleep-dependent theta oscillations in the hum an hippocam pus
and neocortex // J. Neurosci. 2003. V. 23. P. 10897-10903.
C irelli C. The genetic and m olecular regulation o f sleep: from fruit flies to
hum ans // Nat. Rev. Neurosci. 2009. V. 10. No. 8. P. 549-560.

135

Cirelli ., Tononi G. The search for the m olecular correlates o f sleep and
w a k e fu ln e ss// Sleep M edicine Reviews. 2001. V. 5. No. 5. P. 399-410.
Franken P ., Tafti M. Genetics o f sleep and sleep disorders // Frontiers in
Bioscience. 2003. V. 8. P. 381-397.
K im ura ., W inkelmann J. Genetics o f sleep and sleep disorders // Cell. Mol.
Life Sci. 2007. V. 64. P. 1216-1226.
Koh K. et al. Identification o f SLEEPLESS, a Sleep-Prom oting Factor //
Science. 2008. V.321. P. 372-376.
L inkow ski P. EEG sleep patterns in twins // J. Sleep Res. 1999. Suppl 1.
P. 11-13.
L ow rey P. L., Takahashi J. S. M am m alian circadian biology: elucidating
genome-wide levels o f temporal organization // Annu. Rev. Genom ics
Hum. Genet. 2004. V. 5. V. 407-441.
L ugaresi E. et al. Fatal familial insomnia and dysautonom ia with selective
degeneration o f thalamic nuclei // N. Engl. J. Med. 1986. V. 315. P. 9 9 7 1003.
M ackiew icz M. et al. M acrom olecule biosynthesis a key function o f sleep //
Physiol. Genom ics. 2007. V. 31. No. 8. P. 4 41 -4 57.
M ackiew icz M. et al. M olecular m echanism s o f sleep and wakefulness // Ann.
N.Y. Acad. Sci. 2008. V. 1129. P. 335-349.
M aret S. et al. Homer 1a is a core brain molecular correlate o f sleep loss // Proc.
Natl. Acad. Sci. USA. 2007. V. 104. No. 50. P. 20090-20095.
M aret S. et al. Retinoic acid signaling affects cortical synchrony during sleep //
Science 2005. V. 310. P. 111-113.
M ontagna P. et al. Familial and sporadic fatal insomnia // Lancet Neurol.
2003. V. 2. P. 167-176.
Parchi P. et al. Molecular pathology o f fatal familial insomnia // Brain Patho
logy. 1998. V. 8. P. 539-548.
Porkka-H eiskanen T. Gene expression during sleep, wakefulness and sleep
deprivation // Frontiers in Bioscience. 2003. V. 8. P. 421-437.
R eteyJ. V. et al. A functional genetic variation o f adenosine deaminase affects
the duration and intensity o f deep sleep in hum ans // Proc. Natl. Acad. Sci.
USA. 2005. V. 102. P. 15676-15681.
Tafti M. et al. Deficiency in short-chain fatty acid beta-oxidation affects theta
oscillations during sleep // Nat. Genet. 2003. V. 34. P. 320-5.
W isor J. P ., K ild u ff T. S. M olecular genetic advances in sleep research and
their relevance to sleep medicine //S leep. 2005. V. 28. No. 3. P. 357-367.
W u lff ., P orcheret ., C ussans E., F oster R. G. Sleep and circadian rhythm
disturbances: multiple genes and multiple phenotypes // Current Opinion
in Genetics & Development. 2009. V. 19. P. 1-10.

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. . 31. ( , ).
., 1986. . 59-110.
A llada R ., S iegel J. . Unearthing the phylogenetic roots o f sleep // Current
Biology. 2008. V. 18. P. R 670-R 679.
Brow n E. R. et al. Brain and behavioural evidence for rest-activity cycles in
Octopus vulgaris // Behavioural Brain Research. 2006. V. 172. P. 355-359.
C apellini I. et al. Phylogenetic analysis o f the ecology and evolution o f m am
malian sleep // Evolution. 2008. V. 62. No. 7. P. 1764-1776.
C irelli C., B ushev D. Sleep and wakefulness in drosophila m elanogaster //
Ann. N.Y. Acad. Sci. 2008. V. 1129. P. 323-329.
C irelli C., Tononi G. Is sleep essential? // PLoS Biol. 2008. V. 6. No. 8.
P. 1605-1611.
E iland . M ., Lyam in O. /., Siegel J. M. State-related discharge o f neurons in
the brainstem o f freely moving box turtles, Terrapene Carolina Major //
Archive ltal. B iol. 20 0 1 . V. 139. P. 2 3 -3 6 .
F rank M. G. Phylogeny and evolution o f Rapid Eye M ovem ent (REM ) sleep //
Rapid Eye Movement Sleep / B. N. Mallick, S. Inoue (Eds.). New Delhi: Narosa, 1999. P. 17-38.
Jouvet M. REM sleep as a genetic program ming system for physiological indi
vidualization // The Regulation o f Sleep / A. A. Borbely et al. (Eds.). Stras
bourg: HFSP, 2000. P. 171-178.
K avanau J. L. Origin and evolution o f sleep: roles o f vision and endotherm y //
Brain Research Bulletin. 1997. V. 42. No. 4. P. 245-264.
K avanau J. L. REM and NREM sleep as natural accom panim ents o f the evolu
tion o f warm -bloodedness // Neuroscience and Biobehavioral Reviews.
2002. V. 26. P. 889-906.
K avanau J. L. Evolutionary approaches to understanding sleep // Sleep M edi
cine Reviews. 2005. V. 9. P. 141-152.

141

K ild u ff . S. What rest in flies can tell us about sleep in m am m als // Neuron.
2000. V. 26. P. 295-298.
L esku J. A. et a l A phylogenetic analysis o f sleep architecture in mammals: the
integration o f anatomy, physiology, and ecology // The A m erican N atu
ralist. 2006. V. 168. No. 4. P. 4 4 1-4 53.
Lesku J. A. et a l Phylogenetics and the correlates o f m am m alian sleep: A re
appraisal // Sleep M edicine Reviews. 2008. V. 12. P. 229-244.
Lesku J. A. et a l History and future o f comparative analyses in sleep research //
Neuroscience and Biobehavioral Reviews. 2009. V. 33. P. 1024-1036.
Lyam in O. I. et al. Cetacean sleep: A n unusual form o f m am m alian sleep //
Neuroscience and Biobehavioral Reviews. 2008. V. 32. P. 1451-1484.
Lyam in O. /., E ila n d . M , Siegel J. M . Polygraphic and neuronal correlates
o f sleep in freely moving turtles // Sleep. 2002. V. 25. Abstract Suppl.
P. A159.
N icol S. ., A ndersen N. A ., P hillips N. //., B erg er R. J. The echidna manifests
typical characteristics o f rapid eye m ovem ent sleep // Neurosci. Lett. 2000.
V. 283. P. 4 9 - 5 2 .
N icolau . C. et al. Why we sleep: the evolutionary pathway to the m am
malian sleep // Progress in Neurobiology. 2000. V. 62. P. 379-406.
N itz D. A. et a l Electrophysiological correlates o f rest and activity in droso
phila melanogaster // Current Biology. 2002. V. 12. P. 1934-1940.
P enny G., H asegaw a M. The platypus put in its place // Nature. 1997. V. 387.
P. 5 4 9 -5 5 0 .
R attenborg N. C. Evolution o f slow-wave sleep and pall iopallial connectivity
in m am m als and birds: A hypothesis // Brain Research Bulletin. 2006.
V. 69. No 1. P. 2 0-29 .
R attenborg N. C. Avian sleep homeostasis: Convergent evolution o f com plex
brains, cognition and sleep functions in m am mals and birds // Neurosci
ence and Biobehavioral Reviews. 2009. V. 33. P. 25 3-270.
R ial P. K, N icolau . C., G am undi A. et a l The evolution o f waking state //
Sleep and Sleep Disorders: from Molecule to Behavior / O. Hayaishi, S. Inoue
(Eds.). Tokyo: Academ ic Press. 1997. P. 99-112.
R ial P. V., N icolau . ., G am undi A. et a l The trivial function o f sleep //
Sleep M edicine Reviews. 2007. V. 11. P. 31 1-325.
R ial R., N icolau . C., Lopez-G arcia ./. A ., A lm irall H. On the evolution o f
waking and sleeping // Comp. Biochem. Physiol. A. 1993. V. 104. 2.
P. 189-193.
R ial R. V. et al. Evolution o f wakefulness, sleep and hibernation: From reptiles
to m am m als//N eu ro sci. Biobehav. Rev. 2010. V. 34. No 8. P. 1144-1160.
Siegel J. M. Clues to the functions o f m am m alian sleep // Nature. 2005. V. 437.
P. 1264-1271.

142

S ieg el J. M. Do all animals sleep? // Trends in Neurosciences. 2008. V. 31.


No. 4. P. 208-213.
Siegel J. M . Sleep in m onotrem es: implication for the evolution o f REM
sleep // Sleep and Sleep Disorders: from M olecule to Behavior / O. Hayaishi, S. Inoue (Eds.). Tokyo: Acadam ic Press, 1997. P. 113-128.
S iegel J. M. Sleep Phylogeny: Clues to the Evolution and Function o f Sleep //
Sleep: Circuits and Functions. 2005. CRC Press, Boca Raton, FI. P. 163
176.
S iegel J. M. The evolution o f REM sleep // Handbook o f Behavioral State
Control / R. Lydic, H. Bagdoyan (Eds.). Boca Raton: CRC Press, 1999.
P. 87-100.
S ieg el J. ., M anger P. P ., N ienhuis R. e ta l. M onotremes and the evolution o f
REM sleep // Phil. Trans. Roy. Soc. 1998. V. 353. P. 1147-1157.
S iegel J. A/., M anger P. P ., N ienhuis R. et al. REM sleep in the platypus //
Neuroscience. 1999. V .9 1 . P. 391-400.
S ieg el J. A /., M anger P. P ., N ienhuis R. et al. The echidna Tachiglossus aculeatus com bines REM and non-REM aspects in a single sleep state: im
plication for the evolution o f sleep // J. Neurosci. 1996. V. 16. 10.
P . 3500-3506.
S iegel J. M. Sleep viewed as a state o f adaptive inactivity // Nature Reviews
Neuroscience. 2009. V. 10. P. 747-753.
Tohler I. Phylogeny o f sleep regulation // Principles and Practice o f Sleep
M edicine, 4th ed. / Kryger . H., Roth ., Dement W. C., eds. Elsevier:
Am sterdam , 2005. P. 77-90.
van Sw inderen B .,A n d retic R. Arousal in Drosophila //B ehavioural Processes.
2003. V. 64. P. 133-144.
Vertes R. P. Brainstem control o f the events o f REM sleep // Progr. Neurobiol.
1984. V. 22. P. 24 1-288.
Zepelin H ., Siegel J. ., Tohler I. M am m alian sleep // Principles and Practice
o f Sleep Medicine, 4th ed. / Kryger . H., Roth ., Dem ent W. C., eds.
Elsevier: Am sterdam, 2005. P. 91-100.
Zim m erm an J. E. et al. Conservation o f sleep: insights from non-m am m alian
m odel sy ste m s//T re n d s in Neurosciences. 2008. V. 31. No. 7. P. 371-376.

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B ergm ann . ., Everson . ., K ushida . A. et al. Sleep deprivation in the
rat. V. Energy use and mediation // Sleep. 1989. V. 12. P. 31-41.

165

Bergm ann . ., K ushida . ., Everson . A. et al. Sleep deprivation in the


rat. II. M ethodology // Sleep. 1989. V. 12. P. 5-12.
B orhely A. A . Approaches to sleep regulation // Endogenous sleep substances
and sleep regulation / Eds. S. lnoue, A. A. Borbely. Tokyo: Japan Scienti
fic Societies Press, 1985. P. 13-23.
D rum m ond S. P. A. et a l The neural basis o f the psychom otor vigilance task //
Sleep. 2005. V. 28. No. 9. P. 1059-1068.
D rum m ond S. P. A. et al. Sleep deprivation-induced reduction in cortical func
tional response to serial subtraction // Neuroreport. 1999. V. 10. No. 18.
P. 3745-3748.
D rum m ond S. P. A. an d Brown G. G. The effects o f total sleep deprivation on
cerebral responses to cognitive performance. Neuropsychopharmacology.
2001. V. 25. No. S5. P. S68-S73.
D rum m ond S. P. A. et al. Altered brain response to verbal learning following
sleep deprivation. Nature. 2000. V. 403. No. 6770. P. 655-657.
Everson C. A ., Bergm ann . M ., Rechtschaffen A. Hypoalbum inism and ane
mia in totally sleep deprived rats // Sleep research /Eds. M .H . Chase,
D. J. McGinty, C. O Connor. Los Angeles: B1S/BR1, UCLA. 1988. V. 19.
P. 314.
Everson C. A ., B ergm ann H. M ., Rechtschaffen A. Sleep deprivation in the rat.
1 1 1 . Total sleep deprivation // Sleep. 1989a. V. 12. P. 13-21.
Everson C. A ., G illilandM . A ., K ushida C.A. et al. Sleep deprivation in the rat.
IX. Recovery // Sleep. 1989b. V. 12. P. 60-67.
Everson C. A ., W ehr T. A. Nutritional and m etabolic adaptations to prolonged
sleep deprivation in the rat // Am. J. Physiol. Regul. lntegr. Comp. Physiol.
1993. V. 264. P. 376-387.
Everson C. A. Functional consequences o f sustained sleep deprivation in the
rat // Behav. Brain Res. 1995. V. 69. P. 4 3 -5 4 .
Everson C. A ., Toth L. A. Systemic bacterial invasion induced by sleep deprivation //
Am. J. Physiol. Regul. lntegr. Comp. Physiol. 2000. V. 278. V. 905-916.
Everson C. A ., N ow ak Jr. T. S. Flypothalamic thyrotropin-releasing hormone
m R N A responses to hypothyroxinem ia induced by sleep deprivation //
Am. J. Physiol. Endocrinol. Metab. 2002. V. 283. P. 85-93.
Everson C. A., C row ley W. R. Reductions in circulating anabolic horm ones
induced by sustained sleep deprivation in rats // Am. J. Physiol. Endo
crinol. Metab. 2004. V. 286. P. 1060-1070.
Everson C. A ., Laatsch C. D., H ogg N. Antioxidant defense responses to sleep
loss and sleep recovery // Am. J. Physiol. Regul. lntegr. Comp. Physiol.
2005. V. 288. P. 374-383.
Gilliland M .A ., Bergmann . ., Rechtschaffen A. Sleep deprivation in the rat.
Vlll. High EEC amplitude sleep deprivation // Sleep. 1989. V. 12. P. 53-59.

166

G oel N ., B in g es D. F. Genetic resistance to sleep deprivation // Frontiers in


Neuroscience. 2009. V. 3. No. 3. P. 432.
H ennevin ., Leconte P . Etudes des relations entre le sommeil paradoxal et les
processes d acquisition // Physiol. Behav. 1977. V. 18. P. 307-319.
H orne J . A . A review o f the biological effects o f total sleep deprivation in
m an // Biol. Psychol. 1978. V. 7. P. 55-102.
K ovalzon V. M ., Tsibulsky V. L. REM sleep deprivation, stress and emotional
behavior in rats // Behav. Brain Res. 1984. V. 14. P. 2 35-245.
K ushida C. A ., B ergm ann . M , R echtschajfen A. Sleep deprivation in the rat:
IV. Paradoxical sleep deprivation // Sleep. 1989. V. 12. P. 2 2-30 .
M eddis R. The evolution o f sleep // Sleep mechanisms and functions / Ed. A. May
es. Wokingham, Berkshire: Van Nostrand Reinhold, 1983. P. 57-106.
N ailoh P. Sleep deprivation in hum an subjects: a reappraisal // Waking Slee
ping. 1976. V. 1. P. 53-60.
O niani T. N ., Lortkipanidze N. D. Effect o f paradoxical sleep deprivation on
learning and m em ory // ,
-. , 1985. . 136-213.
R echtschajfen ., Bergm ann . . Sleep deprivation in the rat by the diskover-w ater method. // Behav. Brain Res. 1995. V. 69. P. 55-63.
R echtschajfen A ., Bergm ann . M , Everson C. A. et al. Sleep deprivation in
the rat. 1. Conceptual is s u e s // Sleep. 1989a. V. 12. P. 1-4.
Rechtschajfen A ., Bergm ann . M , Everson C. A. et al. Sleep deprivation in
the rat. X. Integration and discussion o f the findings // Sleep. 1989b. V. 12.
P. 68-87.
R echtschajfen A ., G illilandM . A ., Bergm ann . M ., W inter J. B. Physiological
correlates o f prolonged sleep deprivation in rats// Science. 1983. V. 221.
No. 4606. P. 182-184.
R oehrs T ., C arskadon M. A. et al. Daytime Sleepiness and A ltem ess // Prin
ciples and Practice o f Sleep M edicine / Eds. . H. Kryger, T. Roth and
W. C. Dement. Philadelphia: Elsevier Saunders. 2005. P. 39-50.
S piegel K., Tasali E., P enev P., Van C anter E. B rief communication: Sleep
curtailm ent in healthy young m en is associated with decreased leptin le
vels, elevated ghrelin levels, and increased hunger and appetite // Annals
Intern. M ed. 2004. V. 141. No. 11. P. 846-850.
Van L uijtelaar E. L. J. M . Paradoxical sleep: deprivation studies revisited.
Wijchen, Meppel: Krips Repro. 1986.
Vogel G. W., M in ter ., Woolxvine B. Effects o f chronically administrated
drugs on animal behavior // Physiol. Behav. 1986. V. 36. P. 659-666.
Wu J. et al. Prediction o f antidepressant effects o f sleep deprivation by meta
bolic rates in the ventral anterior cingulate and medial prefrontal cortex.
Am. J. Psychiat. 1999. V. 156. P. 1149-1158.

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A xm a ch er N. et al. M em ory processes during sleep: beyond the standard con
solidation theory // Cell. Mol. Life Sci. 2009. V. 66. P. 2285-2297.
B o r n ./., Rasch B., Gais S. Sleep to rem em ber // Neuroscientist. 2006. V. 12.
No. 5. P. 410-424.
Born J., W agner U. M em ory consolidation during sleep. Role o f cortisol feed
b a c k / / Ann. N.Y. Acad. Sci. 2004. V. 1032. P. 198-201.

180

10

C artwright R. D. The role o f sleep in changing our minds: A psychologists


discussion o f papers on m em ory reactivation and consolidation in sleep //
Learn. Mem. 2004. V. 11. P. 660-663.
D iekelm ann S ., B orn J . The m em ory function o f sleep // Nature Reviews
Neuroscience. 2010. V. 11. P. 114-126.
E llenhogen J. M ., P ayne J. D., Stickgold R. The role o f sleep in declarative
m em ory consolidation: passive, permissive, active or none? // Curr. Opin.
Neurobiol. 2006. V. 16. P. 716-722.
Gals S ., B o rn J . Declarative m em ory consolidation: M echanisms acting during
hum an sleep // Learn. Mem. 2004. V. 11. P. 679-685.
K opasz M. et al. Sleep and m em ory in healthy children and adolescents
A critical review // Sleep M edicine Reviews. 2010. V. 14. P. 167-177.
P a ller K. A., Voss J. L. M em ory reactivation and consolidation during sleep //
Learn. Mem. 2004. V. 11. P. 664-670.
R ih eiro S ., N ic o le lis M. A. L. R ev erberation, storage, and po stsy n ap tic p ro
pag atio n o f m em o ries durin g sleep // Learn. Mem. 2004. V. 11. P. 6 8 6 696.
Sheth B. R., Nguyen N., Janvelyan D. Does sleep really influence face re
cognition m em ory? // PLoS ONE. 2009. V. 4. No. 5. P. e5496.
Siegel J. M . The REM sleep m em ory consolidation hypothesis // Science.
2001. V. 294. P. 1058-1063.
Siegel J. M . The incredible shrinking sleep-learning connection // Behavioral
and Brain Sciences. 2005. V. 28. No. 1. P. 82-83.
S ieg el J. M ., Vertes R. P. R eb u ttal//S leep . 2005. V. 28. No. 10. P. 1232-1233.
Stickgold R ., W alker M. P. M em ory consolidation and reconsolidation: what
is the role o f sleep? // Trends in Neurosciences. 2005. V. 28. No. 8.
P . 4 08-415 .
Stickgold R ., W alker M P. Sleep-dependent m em ory consolidation and recon
solidation // Sleep Medicine. 2007. V. 8. P. 331-343.
Vertes R. P., Eastm an . E. The case against m em ory consolidation in REM
sleep // Behav. Brain Sci. 2000. V. 23. No. 6. P. 867-876.
Vertes R. P. M emory consolidation in sleep: dream or reality // Neuron. 2004.
V. 44. P. 135-148.
Vertes R. P. Sleep is for rest, waking consciousness is for learning and m em ory
o f any kind // Behav. Brain Sci. 2005. V. 28. P. 86.
Vertes R. P., Siegel J. M. Tim e for the sleep comm unity to take a critical look
at the purported role o f sleep in m em ory processing // Sleep. 2005. V. 28.
No. 10. P. 1228-1229.

181

W alker . P. A refined m odel o f sleep and the time course o f m em ory form a
tion // Behav. Brain Sci. 2005. V. 28. P. 51-6 4. Discussion. P. 64-104.
W alker M. P. REM, dreams and emotional brain homeostasis // Front. N euro
sci. 2009. V. 3. No. 3. P. 442-443.
W alker M. P., Stickgold R. Sleep-dependent learning and m em ory consoli
dation // Neuron. 2004. V. 44. P. 121-133.
W alker M. P., Stickgold R. Sleep, m em ory, and plasticity // Annual Review
o f Psychology. 2006. V. 57. P. 139-66.
W alker . P ., Stickgold R. Overnight alchemy: sleep-dependent m em ory ev o
lution // Nature Reviews Neuroscience. 2010. V. 11. P. 218-219.
Wins on J. To sleep, perchance to dream // Learn. Mem. 2004. V. 11. P. 659.

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Arzl ., H olsboer F. CRF signaling: m olecular specificity for drug targeting
in the C N S // Trends in Phannacological Sciences. 2006. V. 27. No. 10.
P. 532-538.
Balbo ., L ep ro u ll R., Van C auter E. Impact o f sleep and its disturbances
on hypothalamo-pituitary-adrenal axis activity // International Journal o f
Endocrinology. 2010. Article ID 759234. Doi: 10.1155/2010/759234.
B randenberger G. et al. Twenty-four-hour profiles o f plasma renin activity
in relation to the sleep-wake cycle. J. Hypertens. 1994. V. 12. P. 277-283.
Buxton . ., Spiegel K. and Van C auter E. M odulation o f endocrine func
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P. 59-70.
D zaja A. et al. W om ens sleep in health and disease // Journal o f Psychiatric
Research. 2005. V. 39. P. 55-76.
Lejeune-Lenain C. el al. Control o f circadian and episodic variations o f adre
nal androgen secretion in m an // J. Endocrinol. Invest. 1987. V. 10.
P. 267-275.

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O bal F. (Jr.), K ru eg er J. M. G H R H and sleep // Sleep M edicine Reviews.


2004. V. 8. P. 367-377.
Steiger A. Sleep and the hypothalam o-pituitary-adrenocortical sy stem // Sleep
M edicine Reviews. 2002. V. 6. No. 2. P. 125-138.
Steig er A. Sleep and endocrine regulation // Frontiers in Bioscience. 2003.
V. 8. P. s358-s376.
Steiger A. Sleep and endocrinology // Journal o f Internal Medicine. 2003.
V. 254. P . 13-22.
Steig er A . Neurochemical regulation o f sleep // Journal o f Psychiatric Re
search. 2007. V. 41. P. 537-552.
Van C anter E., C opinschi G. Endocrine and other biological rhythm s // Endo
crinology, 5th edition / Eds. L.J.Degroot, J.L. Jam eson. Elsevier Saunders:
Phildelphia. 2006. V. 1. P. 341-372.
Van C a u terE . et al. Modulation o f glucose regulation by circadian rhythmicity
and sleep // J. Clin. Invest. 1991. V. 88. P. 934-942.
Van C anter E., Spiegel K. Circadian and sleep control o f hormonal sec
retions // Regulation o f sleep and circadian rhythm s / Eds. P. C. Zee,
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Marcel Dekker: N. Y. 1999. P. 397-426.

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