Neurochemistry of Sleep and Wakefulness Edited by Jaime M

Cambridge University Press 978-0-521-86441-1 - Neurochemistry of Sleep and Wakefulness Edited by Jaime M. Monti, S. R. Pandi-Perumal and Christopher M. Sinton Index More information

Index

5-HT (5-hydroxytryptamine) full agonists at 5-HT7 receptor see serotonin postsynaptic effects of receptor 5-HT receptors 32 receptors 260 antagonists 264--5 classiﬁcation 252 operational operational distribution 253, 254, characteristics characteristics 256, 255, 256--7 253--4 257 operational role in sleep–wake 5-hydroxytryptamine see 5-HT characteristics modulation 260 receptors; serotonin

252--6 5-HT2A receptor, operational subtypes involved in characteristics 254, acetylcholine sleep–wake 255 and REM sleep

regulation 252 5-HT2A/2B/2C receptors regulation 66

5-HT1A receptor distribution 261 degradation following

effects of selective effects of 5-HT2 receptor release 26 serotonin reuptake agonists 261 discovery of

inhibitors 259--60 effects of 5-HT2 receptor neurotransmitter full agonists at antagonists 261--2, activity 26, 109, autoreceptors and 263 110 partial agonists at role in sleep–wake distribution of postsynaptic regulation 261--3 cholinergic neurons

receptors 259 5-HT2C receptor, operational 25, 26--7 full agonists at pre- and characteristics 254, effects of blocking postsynaptic 255 degradation 109--11

receptors 257--9 5-HT3 receptor effects on target organs operational effects of receptor 27 characteristics agonists and extent of 252--3 antagonists 263--4 neurotransmitter role in sleep–wake operational activity 109, 110 modulation characteristics 256 formation 26 257--60 role in sleep–wake muscarinic receptors

5-HT1B receptor regulation 263--4 27--8

462

© Cambridge University Press www.cambridge.org Cambridge University Press 978-0-521-86441-1 - Neurochemistry of Sleep and Wakefulness Edited by Jaime M. Monti, S. R. Pandi-Perumal and Christopher M. Sinton Index More information

Index 463

nicotinic receptors 27--8 role in PGD sleep signal adenosine as a homeostatic receptor subtypes 27--8 transduction 372--4 sleep factor 339--40 release across behavioral role in the sleep–wake in vivo measurements states 27 cycle 44--5 341--2 release in the pontine adenosine agonists and possible applications in reticular formation antagonists, effects sleep disorders during REM sleep of 339--40 352--3 110, 113, 119--21, 122 adenosine and sleep adenosine formation role in wakefulness and deprivation and brain energy REM (paradoxical) cause of rise in metabolism 342--3 sleep 26, 27--8, 90--1 adenosine 346--7 extracellular adenosine see also cholinergic effects of energy 343--5 neurons imbalance 346--7 intracellular adenosine acetylcholine release, effects of NO 346--7 342--3 modulation by source of increased adenosine hypnogenic action

muscarinic adenosine 345--6 case for A1R-mediated cholinergic adenosine and vigilance action in the BF autoreceptors 110, 339--41 347--9

113, 121--9 effects of adenosine case for A2AR-mediated acetylcholine research, agonists and action in the VLPO clinical relevance antagonists 339--40 349, 350--2 133--4 effects of adenosine neural mechanisms acetylcholine transporter receptor agonists 347--9, 350--2 blockade, effects on and antagonists adenosine kinase inhibitors REM sleep 110, 130, 339--41 343--4, 345, 352 131 effects of caffeine adenosine metabolism acetylcholinesterase (AChE) 340--41 343--4 26 effects of nucleoside control of extracellular acetylcholinesterase transporter adenosine levels inhibitors, effects inhibitors 340 343--5 on REM sleep adenosine antagonists, adenosine receptor agonists 112--16 pharmacology and antagonists, active and rest phases, 442--7 effects of 339--41 mechanism for adenosine applications in adenosine receptors

alternation between sleep disorders A1 (A1R) 338--9

59--60 352--3 A2A (A2AR) 338--9

active sleep see REM sleep adenosine kinase A2B (A2BR) 338--9

adenosine inhibitors 352 A3 (A3R) 338--9

neurotransmitter effects of caffeine case for A1R-mediated activity 44--5 352 action in the BF physiology 338 nucleoside transporter 347--9

range of functions 338 blockade 352--3 case for A2AR-mediated role in energy potential side-effects action in the VLPO metabolism 44--5 352 349, 350--2

464 Index

adenosine receptors (cont.) animal studies of integration in the classification 338--9 neurotransmitters hypothalamus targets for stimulants 24 426--7 45 anticonvulsant effects of atypical antipsychotics adenosine sleep factor melatonin 290 440 16--17 antidepressants and sleep automatic behaviors 405, adenosine triphosphate (ATP) 435--8 406 and neuronal cAMP regulated autoreceptors, definition 110, metabolism 44--5 pathways 435--6 121 see also role in energy sleep and depression muscarinic metabolism 44--5 436--8 cholinergic adrenaline (epinephrine) sleep–wakefulness autoreceptors discovery of 32--3 effects of first synthesis 179--80 generation barbiturates 433--4 see also catecholamines compounds 156 basal forebrain (BF)

African sleeping sickness antioxidant properties of case for A1R-mediated 366 melatonin and action in 347--9 age, variation in REM sleep its metabolites effects of glutamate 61 284--5 neurotransmission age-related circadian antipsychotic medications 227 changes, melatonin and sleep 438--40 basal forebrain cholinergic treatment 294 arousal neurons 26--9 ageing and sleep 443--5 effects of orexin activity levels 27 ageing population, clinical deficiency 404, distribution 25, 26--7 relevance of ACh 419--20 functions 28--9 research 133--4 in orexin- and orexin basal forebrain GABAergic agomelatine 299--300, receptor-deficient neurons 40--1 301 rodents 415 basal forebrain NO-ergic aminergic neurons, rates of role of melanin- mechanisms 326--7 firing in sleep–wake concentrating basal forebrain sleep-active regulation 250--2 hormone (MCH) neurons 6 AMPA glutamate receptors 426 BenzedrineTM 440--1 225 arousal systems benzodiazepine receptors amphetamines 440--1 effects of sleep-active 433--4 amphibians, brain electrical WSNs 13, 14 benzodiazepines 433--5 activity in rest state efferents from POA areas of the brain 60--1 sleep-active neurons involved 434--5 anesthesia, effects on the 8, 9 effects on sleep 434, prefrontal cortex GABAergic control 7, 435 125, 126 10, 11, 12 GABAergic regulation anesthetics 433--4 GABAergic projections 434--5 animal models, and the from POA tolerance and nature of cataplexy sleep-active neurons dependence 435 416--18 8, 9 beta-trace biomarker 368--9

Index 465

biochemical investigation of pharmacology 441--7 chemical sampling of neurotransmitters sleep effects 352 neurotransmitters 23--4 cancer, exogenous 23--4 birds, REM sleep 60--1 administration of choline acetyltransferase blind people, circadian melatonin 283 (ChAT) 26--7 rhythm problems cataplexy choline transporter blockade, 294 distinctions across effects of REM sleep body temperature, and sleep species 416--18 110, 129--30 propensity 10--14 findings from animal cholinergic basal forebrain Borbély’s two-process theory models 416--18 neurons 26--9 of sleep–wake and LC neuron activity activity levels 27 regulation 337 34 functions 28--9 brain energy metabolism, nature of 416--18 cholinergic brainstem and adenosine possible causes 95 neurons 26--9 formation 342--3 role of histamine cholinergic LDT/PPT neurons brain imaging techniques neurons 38 activity levels 27 (MRI, PET) 24 role of orexin production of NO 28 brain regions controlling (hypocretin) cholinergic medial septum REM sleep 24--6 neurons 38--9 neurons, functions brain regions controlling as symptom of 28--9 wakefulness 24--6 narcolepsy 38--9 cholinergic neurons brainstem symptoms and distribution 25, 26--7 effects of glutamate treatment 33, rates of firing in neurotransmission 403--5, 406 sleep–wake 225--6 see also regulation 250--2 mechanisms which narcolepsy–cataplexy see also acetylcholine mediate NO actions catecholamine cell groups, cholinergic synapse (brain) 325--6 classification 110, 121 brainstem cholinergic 183--4, 191 cholinergic synapse neurons 26--9 catecholamines mechanisms 109, distribution 25, 26--7 actions on sleep 33--4 110 buspirone 259 biosynthetic pathway effects of blocking ACh 33, 179--80 degradation 109--11 c-Fos immunoreactivity depletion by reserpine circadian changes, marker 3--4, 374 33 age-related 294 caffeine see also adrenaline; circadian clock genes, role in adenosine antagonist dopamine; control of dopamine 373--4 noradrenaline systems 186 adenosine receptor cerebral cortex, acetylcholine circadian control of targets 45 release 27 histamine synthesis effects of 340--1 chemical lesion techniques and release 146--7 non-specific adenosine 24 circadian pacemaker receptor antagonist chemical neurotransmission, (suprachiasmatic 340--1 discovery of 26 nucleus) 186

466 Index

circadian pattern of cold-sensitive neurons (CSNs) and REM sleep melatonin secretion in the POA regulation 65 285--6 13--14 catabolic pathways 182 circadian phase-shifting cortex, effects of glutamate cell loss 179 effects of melatonin neurotransmission cellular and subcellular 293--4 227--8 effects 182--3 circadian process, cortical activation during influence on wake–sleep sleep–wake wakefulness 145 behaviors 179 regulation 337 cortical synchronization, metabolism 182 circadian rhythms effects of cortistatin neuromodulatory body temperature and 392--4 physiological effects sleep 10--13 cortistatin 182--3 disruption by light 194 and sleep–wake neurotransmitter problems in blind regulation 392--4 activity 44 people 294 discovery 392 range of functions in circadian sleep disorders, effects on cortical the CNS 179 benefits of synchronization reuptake from the exogenous 392--4 synapse 180--2 administration of effects on slow wave role in control of melatonin 283 sleep 392--4 wakefulness 44 circadian wakefulness signal, receptors 392 synthesis 179--80, effects of orexin structure 392 181 deficiency 420--2 synthesis 392 see also catecholamines; citalopram 260 cyclopyrrolones 434 Parkinson’s disease clinical effects of cytokines, as sleep factors dopamine-acting drugs dopaminomimetics 316 440--1 190, 193--4 dopamine circuits in the clinical potential of daytime sleepiness, in brain glutamate receptor Parkinson’s disease axon collateralization agonists/antagonists 202--5 185 239--40 delayed sleep phase classification 183--4, 191 clinical relevance of ACh syndrome, functional anatomy research 133--4 melatonin 183--5, 191 CNS stimulants and sleep treatment 294 mesocorticolimbic 440--50 depression pathway 184 adenosine antagonists and sleep 436--8 nigrostriatal pathway 442--7 antidepressants and 184 caffeine 441--7 sleep 435--8 subparafascicular dopamine-acting drugs depression treatments thalamus cell group 440--1 (serotonin-related) 185 modafinil and 31 tuberohypophyseal wakefulness 447--8 diseases, effects on REM pathway 184--5 nicotine 448--50 sleep 61 tuberoinfundibular cocaine 440--1 dopamine pathway 184--5

Index 467

dopamine modulation of dopamine signaling afferent connections wake–sleep state behavioral state 249, 250 190--200 influences on 188, efferent connections activation of dopamine 189--90 247--8, 249 receptor subtypes circadian influences on rates of firing in 193--4 186--9 sleep–wake affinity of stimulants for diurnal variations in regulation 250--2 DAT 190, 192 186--9 animal studies 200--2 homeostatic influences EEG (electroencephalogram) clinical effects of on 189 24 dopaminomimetics role of circadian clock activation by blocking 190, 193--4 genes 186 ACh degradation exogenous dopamine transporter (DAT) 109--11 dopaminomimetic 44, 180--2 activity during REM effects 181, 192--4 affinity of stimulants sleep 109--11 functional anatomy of 190, 192 activity during mesotelencephalic genetic modification of wakefulness 145 dopamine neurons DAT function 190, in mammalian species 195--200 192--3 60--1 genetic modification of dopaminergic D-1 and D-2 EEG excitability, DAT function 190, receptor antagonists autoreceptor 192--3 439--40 modulation of ACh light disruption of dopaminergic inputs to TMN 110, 123--9 circadian rhythms histaminergic electrical lesion techniques 194 neurons 150 24 mesotelencephalic dopaminomimetics electrographic recording system 190--2 clinical effects 190, techniques (EEG, pharmacological 193--4 EMG, EOG) 24 evidence 181, effects on REM sleep electrophysiological 192--4 200 investigations of physiology of effects on wake–sleep neurotransmitters mesotelencephalic state 181, 192--4 23--4 dopamine neurons sleep-related side effects EMG (electromyogram) 24 188, 194--5 200 in mammalian species role of midbrain dorsal raphe nucleus (DRN) 60--1 dopaminergic chemoarchitecture energy balance neurons 200--2 250 influence on sleep–wake dopamine receptors efferents from POA regulation activation of subtypes sleep-active neurons 424--7 193--4 8 role of melanin- characteristics of GABA release during concentrating subtypes 182--3 sleep 7, 10 hormone (MCH) classification of subtypes dorsal raphe serotonergic 424 182 neurons 247 role of orexin 424

468 Index

EOG (electrooculogram) 24 possible source 7, 10 gaboxadol 435 in mammalian species GABA shunt 41 galanin inputs to TMN 60--1 GABA-A receptor complex histaminergic epilepsy in children, effects 434 neurons 150 of melatonin 290 GABA-A receptors genetic engineering epinephrine see adrenaline and sleep 433--5 approaches to estradiol, effects on location 434 neurotransmitter melatonin receptors subunits 434 study 24 289--90 GABAergic activity, effects of gepirone 259 excessive daytime sleepiness melatonin 295--9, ghrelin 403--5, 406 300 role in sleep–wake excessive nocturnal GABAergic basal forebrain regulation 318--21, movement, in neurons 40--1 322, 323 Parkinson’s disease GABAergic brainstem sources in the body 202, 203, 205--6 neurons, role in 318 REM sleep 35, 42 structure 318, 319 flip–flop sleep switch model GABAergic control of arousal see also 40, 41--2 systems 7, 10, 11, orexin–ghrelin–NPY interaction of orexin 12 circuit (hypocretin) and GABAergic drugs glutamate MCH 426 benefits and limitations interplay with GABA proposed role of orexin 224 224--5 (hypocretin) sleep-related side effects metabolism 43--4 neurons 391 224 neurotransmitter role of neuropeptide S GABAergic inhibition based activity 43--4, (NPS) 395--6, 397 model of REM sleep 224--5 role of POA sleep-active regulation 69--70, role in paradoxical sleep neurons 14 71 89--90 fluoxetine 260, 437--8 GABAergic inputs to TMN glutamate histaminergic neurotransmission GABA (␥-amino-butyric acid) neurons 150 basal forebrain 227 and REM sleep GABAergic neurons brainstem 225--6 regulation 66--8 distribution 40--1 cortex 227--8 discovery 40 gating paradoxical sleep hypothalamus GABA high affinity onset 88--9 226--7 transporter 41 inhibition of in brain areas important GABA synthesis 41 monoaminergic for sleep and POA sleep-active neurons neurons in PS 91--4 arousal 225--8 4, 5 POA neurons 40--1 in brain areas which GABA receptors 41 roles in sleep–wake regulate vigilance actions of sedative control 35, 42--3 225--8 hypnotic drugs 17 GABAergic POA projections lateral and dorsomedial GABA release during sleep to arousal systems hypothalamus locations 5, 10, 11, 12 8, 9 226--7

Index 469

medial preoptic area of kainate 225 synthesis in the CNS the hypothalamus metabotropic 225 146--7 227 NMDA 225 turnover in the brain medulla 225--6 glycine 146, 147 orexin (hypocretin)- formation 43 histamine and containing neurons high afﬁnity transporter sleep-wakefulness 226--7 system 43 studies 156--66

pedunculopontine mode of action 43 H1 receptor agonists/ tegmentum (PPT) neurotransmitter antagonists 226 activity 43 162--3

pons 225--6 role in REM muscle H2 receptor agonists/ pontine reticular atonia 43 antagonists 163

formation 225--6 glycinergic neurons, H3 receptor agonists/ suprachiasmatic nucleus distribution 43 antagonists 163--5 226 HA administration thalamus 227--8 hallucinations 405, 406 161--2 glutamate receptor haloperidol 438 biochemical and agonists/antagonists histamine (HA) molecular studies clinical potential and behavior 156 158--60 239--40 and REM sleep c-Fos indication of TMN competitive AMPA regulation 65--6 neuronal activity receptor antagonist circadian control of 159--60 235 synthesis and early work 156--7 competitive NMDA release 146--7 effects of ﬁrst receptor antagonist discovery 36 generation 234--5 discovery of antihistamines 156 effects on brain arousal neurotransmitter electrophysiological 228--40 activity 36, studies 157--8 effects on sleep and EEG 145--6 HDC (L-histidine 228--40 in brain mast cells 37 decarboxylase) ionotropic receptor inactivation by knockout mice manipulations catabolism 146, 160 228--35 147 inactivation or lesion of metabotropic receptor levels in the brain the TMN 165--6 manipulations 146--7 manipulation of HA 235--9 neuronal pool in the synthesis and noncompetitive NMDA brain 146, 147 degradation 161 receptor antagonists non-neuronal pool in measurement of HA 228--34 the brain (mast release and potential use in sleep cells) 146 turnover 158--9 disorders 239--40 receptors 37 pharmacological studies glutamate receptors 44, 225 role in the sleep–wake 161--6 AMPA 225 cycle 37--8 role of the posterior ionotropic 225 synthesis 30, 36--7 hypothalamus 157

470 Index

histamine neurons see adenosine 16--17 ionotropic glutamate histamine TMN IL-1␤ 16 receptors 225 (tuberomammillary PGD2 17 manipulations 228--35 nucleus) neurons see also sleep factors ipsapirone 259 histamine receptors hypnotics 433--5 153--6 hypocretin see orexin jet lag symptoms, melatonin

H1 receptor 153--4 (hypocretin) treatment 293--4

H2 receptor 154--5 hypothalamic preoptic area

H3 receptor 155--6 (POA) see preoptic kainate glutamate receptors

H4 receptor 153 area (POA) 225 subtypes classification hypothalamus 153 discovery of orexins lateral and dorsomedial histamine TMN (hypocretins) hypothalamus, (tuberomammillary 388--9 effects of glutamate nucleus) neurons distinct functions of the neurotransmission 36--8, 147--8 various nuclei 226--7 activity levels 37--8 388--9 lateral hypothalamus (LH) localization in the TMN effects of glutamate integration of arousal 37 neurotransmission systems 426--7 method of release of 226--7 role in sleep–wake histamine 37 integration of arousal regulation rates of firing in systems 426--7 424--6 sleep-wake location of GABA-A LC see locus coeruleus regulation 250--2 receptors 434 LDT/PPT (laterodorsal homeostatic control of sleep, tegmentum/ role of the POA imidazopyridines 434 pedunculopontine hypnogenic system immune function disorders tegmentum) 15 283 cholinergic neurons homeostatic process, immunohistochemical 25, 26--7 sleep–wake investigation of activity levels 27 regulation 337, neurotransmitters production of NO 338 23--4 28 homeostatic sleep factors, insomnia light/dark cycle, influence on adenosine 339--40, exogenous melatonin secretion 341--2, 352--3 see also administration of 285--6 sleep factors melatonin 283 lithium 436 humoral theory of sleep genetic influences locus coeruleus (LC) regulation 445--6 GABA release during 363 interferon alpha 2, as a sleep sleep 7, 10 hypnogenic mechanism, in factor 316 projections from POA the hypothalamic interleukin 1 (IL-1) sleep sleep-active neurons POA 3 factors 316 8 hypnogenic sleep factors interleukin-1␤ (IL-1␤) sleep role in REM sleep 15--17 factor 16 generation 61--3

Index 471

locus coeruleus efferent connection therapeutic exogenous noradrenaline 247--8, 249 administration 283 neurons 32--4 medulla, effects of glutamate use in pediatric epilepsy actions on sleep 33--4 neurotransmission 290 activity levels 33--4 225--6 melatonin agonists distribution 33 melanin-concentrating agomelatine 299--300, LY 156735 (melatonin hormone (MCH) 301 agonist) 301 inﬂuence on sleep-wake LY 156735 301 regulation 424--7 ramelteon (RozeremTM) mammals, REM sleep 60--1 interaction with orexin 300--1, 435 mastocytosis 366 424--6 use in treatment of MCH (melanin concentrating MCH–/–; orexin–/– (double sleep disorders hormone) neurons, knockout) mice 299--301 role in paradoxical 424--6 melatonin metabolism sleep 96--7 role in arousal 426 286--7 MCH–/–; orexin–/– (double role in energy balance antioxidant properties knockout) mice 424 of metabolites 424--6 role in the sleep switch 284--5 medial pontine reticular 426 melatonin modulation of formation, effects of melatonin human sleep autoreceptor antioxidant properties 290--1 modulation of ACh 284--5 circadian phase-shifting 110, 123--5 biosynthesis 283--4 effects of melatonin medial preoptic area of the chemical nature 283 293--4 hypothalamus, circulation and half life effects of endogenous effects of glutamate 284 melatonin neurotransmission discovery 283 administration 227 functions 287 291--4 medial septum cholinergic inﬂuence of light/dark neuropharmacological neurons cycle 283 mechanisms distribution 25, 26--7 mechanism of action 295--9, 300 functions 28--9 287--9 opening of the sleep median preoptic nucleus metabolism 284--5 gate 290--1 (MnPN) mood stabilizing and treatment of age-related efferents to arousal anticonvulsant circadian changes systems 8, 9 effects 290 294 neuronal projections to pineal gland treatment of circadian the PLH 4 biosynthesis and rhythm problems in sleep-active neurons secretion 283 blind people 294 3--4, 5, 6 possible modulation of treatment of delayed median raphe serotonergic GABAergic activity sleep phase neurons 247 295--9, 300 syndrome 294 afferent connections receptor binding 287--9 treatment of jet lag 249, 250 secretion 283, 284 symptoms 293--4

472 Index

melatonin modulation of midbrain dopaminergic mutual inhibitory model of human sleep (cont.) neurons, role in REM sleep treatment of sleep regulation of regulation 69 disorders 291--4 wake–sleep state wake-maintenance zone 200--2 narcolepsy (‘‘forbidden zone”) mioflazine 340 and LC neuron activity 291 mirtazapine 437--8 34 melatonin receptors modafinil and wakefulness link with orexins effects of clinically 447--8 (hypocretins) 389 administered drugs molecular biological study of pharmacology of 289--90 neurotransmitters orexins functions 287--9 24 (hypocretins) 450--1 regulation 289--90 monoamine oxidase possible causes 95 melatonin secretion inhibitors (MAOIs) role of orexin circadian pattern 31, 33, 435--6 (hypocretin) 285--6 monoaminergic systems, neurons 38--9 control by the activity during side effects of suprachiasmatic wakefulness dopaminomimetics nucleus 285--6 145 200 influence of light/dark monoaminergic theory of symptoms 38--9 cycle 285--6 sleep and waking treatments 33 interindividual 31--2 narcolepsy–cataplexy, in differences 286 mood stabilizers 436 orexin- and orexin regulation 285--6 effects of melatonin receptor-deficient up-regulation 286 290 rodents 415 mesocorticolimbic dopamine muramyl peptides (Factor S) narcolepsy–cataplexy in pathway 184 315--16 humans 403--9 mesotelencephalic system muscarinic acetylcholine and loss of orexin 190--2 receptors 27--8 signaling 407--9 functional anatomy of muscarinic cholinergic automatic behaviors dopamine neurons autoreceptors, 405, 406 195--200 modulation of ACh cataplexy symptoms and physiology of dopamine release 110, 113, treatment 403--5, neurons 188, 194--5 121--9 406 metabotropic glutamate muscarinic cholinergic clinical diagnosis 405--7 receptor 225 receptors disruption of sleep–wake manipulations 235--9 autoreceptor subtype regulation 405--7 methylphenidate 440--1 123, 124 excessive daytime methylxanthines, adenosine role in REM sleep sleepiness 403--5, receptor targets 45 generation 115, 406 mianserine 437 116--18 fragmented nocturnal microdialysis– subtypes 116--18 sleep 405, 406, electrochemical muscle atonia in REM, role 409 detection 23--4 of glycine 43 hallucinations 405, 406

Index 473

signs and symptoms source in the brain reciprocal interaction 403, 406 321 model of REM sleep sleep paralysis 405, 406 structure 319, 34--6 narcolepsy-like phenotype in 321 neurotransmitters for REM Parkinson’s disease see also orexin–ghrelin– sleep regulation 202--5 NPY circuit 63--70 network model of PS onset neuropeptides and acetylcholine 66 and maintenance sleep–wake dopamine 65 97--8 regulation GABA 66--8 neurochemical regulatory cortistatin 392--4 GABAergic inhibition mechanisms, POA hypocretins (orexins) based model sleep-active neurons 388--91 69--70, 71 15--17 neuropeptide S (NPS) histamine 65--6 neurodegenerative diseases, 395--6, 397 interactions between benefits of study methods 388--9, 68--70 exogenous 392, 396 mutual inhibitory administration of suitability as sleep model 69 melatonin 283 circuit modulators noradrenaline 63--4 neuromodulator sleep 396--7 orexin (hypocretin) factors 317--18 urotensin II 394--5 68 neuronal metabolism, and use of reverse genetics reciprocal interaction ATP 44--5 to study 388--9, model 68--9 neurons 392, 396 serotonin 65 electrical properties 24 neurotransmitter nicotine, effects on sleep generation of electrical metabolism 24 131--2, 448--50 signals 23 neurotransmitter sleep nicotinic acetylcholine neuropeptide S (NPS) factors 317--18 receptors 27--8 and sleep–wake neurotransmitter systems nicotinic cholinergic regulation 395--6, investigative receptors 397 methodologies role in arousal state and the sleep switch 23--4 control 131--2 (flip–flop) model involvement in structure 131 395--6, 397 sleep–wake stages subtypes 131 anxiolytic properties 433 nigrostriatal dopamine 395, 396 neurotransmitters pathway 184 promotion of animal studies 24 nitric oxide (NO), production wakefulness 395--6, cortical activation by LDT/PPT 397 during wakefulness cholinergic neurons neuropeptide S (NPS) 145 28 receptor 395 discovery 24 nitric oxide (NO) as a sleep neuropeptide Y (NPY) discovery of chemical factor role in sleep–wake neurotransmission actions in the regulation 319, 26 suprachiasmatic 321--2, 323 functions 23 nucleus 327--8

474 Index

nitric oxide (NO) (cont.) effects of orexin 322, 323, 388--91, basal forebrain NO-ergic deficiency 422 424--7 mechanisms 326--7 noradrenaline (NA) and the gating of REM brainstem mechanisms (norepinephrine) sleep 418--19 which mediate NO and REM sleep discovery 38, 388--9 actions 325--6 regulation 63--4 integration into the diurnal rhythm of NOS biosynthetic pathways reciprocal activity 327 33 interaction model dynamics of NO release discovery of 32--3 389--91 327 discovery of interaction with MCH effects in sleep neurotransmitter 424--6 deprivation 346--7 activity 32--3 link with narcolepsy effects of NOS inhibitors enhancement of 389 324 extracellular pharmacology 450--1 formation by nitric concentration 33 role in energy oxide synthase increase during REM homeostasis 424 (NOS) 322--3 sleep deprivation structure and formation isoforms of nitric oxide 71--3 38 synthase (NOS) receptors 34 wake-promoting effects 322--3 synthesis 179--80 389--1 neurotransmitter noradrenaline LC neurons orexin- and orexin functions 322 32--4 receptor-deficient NO donor studies actions on sleep rodents 324--5 33--4 effects on arousal role in sleep–wake activity levels 33--4 415 regulation 322--8 noradrenaline neurons effects on REM sleep studies of NOS-deficient distribution 33 415--16 transgenic mice rates of firing in MCH–/–; orexin–/– (double 326 sleep–wake knockout) mice nitric oxide synthase (NOS) regulation 250--2 424--6 322--3 noradrenaline reuptake nature of cataplexy NMDA glutamate receptors transporter (NERT) 416--18 225 33 orexin/ataxin-3transgenic nocturnal sleep, fragmented nucleoside transporter mice and rats 405, 406, 409 inhibitors 340, 413--14, 416--18 non-mammalian species, 352--3 orexin−/−mouse brain electrical phenotype 409, activity in rest state obestatin 321 410--13 60--1 olanzapine 438, 439 orexin receptor null non-REM (NREM) sleep (slow orexin (hypocretin) mice 414--15, wave sleep) 60 and REM sleep 418--19, 424 effects of autoreceptor regulation 68 phenotypic modulation of ACh and sleep–wake characterization 125, 126 regulation 318, 409--11, 416

Index 475

requirements for rates of firing in studies 85--6 see also narcolepsy– sleep–wake REM sleep cataplexy regulation 250--2 paradoxical sleep (PS) onset 415 receptors 38 and maintenance requirements for REM role in cataplexy 38--9 GABAergic inhibition of sleep dysregulation role in narcolepsy 38--9 monoaminergic 415 role in paradoxical sleep neurons 91--4 orexin–ataxin–3 transgenic 95--6, 97 GABAergic neurons mice and rats role in the sleep–wake gating onset 88--9 413--14, 416--18 cycle 39, 40 network model 97--8 orexin deficiency and orexin (hypocretin) pontine structures abnormal sleepiness neuropeptide affecting 85--6 404, 419--24 system 402--3, 404 reciprocal interaction abnormal regulation of actions 403 model 86--8 non-REM sleep discovery of orexins role of acetylcholine 422 (hypocretins) 402, 90--1 arousal deficit 404, 403, 404 role of glutamate 419--20 narcolepsy–cataplexy in 89--90 consequences of orexin humans 403--9 role of MCH peptidergic signaling deficiency prepro-orexin neurons 96--7 424 (prepro-hypocretin) role of orexin effects on the circadian gene 402, 403, 404 (hypocretin) wakefulness signal projection of orexin neurons 95--6, 97 420--2 neurons 403, 404 role of the posterior fragmentation of receptors 403 hypothalamus (PH) vigilance states structure 402, 403, 404 95, 96--7 422--4 orexin (hypocretin) receptor role of the orexin–ghrelin–NPY circuit null mice 414--15, sublaterodorsal 318--22, 323 418--19, 424 nucleus (SLD) orexin–/–mouse phenotype orexin (hypocretin) receptors 88--91 orexin (hypocretin) neurons 403 structures involved activity during states of orexinergic inputs to TMN 94--7 vigilance 391 histaminergic Parkinson’s disease (PD) activity levels 39, 40 neurons 150 daytime sleepiness distribution 38 oxidative damage, benefits of 202--5 effects of glutamate exogenous effects of dopamine cell neurotransmission administration of loss 179 226--7 melatonin 283 excessive nocturnal in the perifornical movement 202, hypothalamus 38--9 pain relief, clinical relevance 203, 205--6 proposed role in the of ACh research narcolepsy-like sleep–switch 133--4 phenotype 202--5 (flip-flop) model paradoxical sleep (PS), periodic leg movements 391 discovery and early 202, 203, 205--6

476 Index

Parkinson’s disease (cont.) in Parkinson’s disease GABA-A receptors and REM sleep behaviour 202, 203, 205--6 sleep 433--5 disorder 202, 203, peripheral vasculature, effect gaboxadol 435 205--6 of urotensin II genetic influences in side-effects of treatment 394--5 insomnia 445--6 200 PG see prostaglandin haloperidol 438 sleep disorders 440 PGO (pons, lateral geniculate hypnotics 433--5 sleep-onset REM periods nucleus, occipital imidazopyridines 434 (SOREMs) 202--5 cortex) waves 27 lithium 436 sleep-related effects of PGO spikes methylphenidate dopaminomimetics and PCPA 32 440--1 200 and serotonin 32 mianserine 437 state-related dysfunction pharmacological mirtazapine 437--8 202--6 investigation of modafinil and substrates underlying neurotransmitters wakefulness excessive nocturnal 23--4 447--8 movement 205--6 pharmacology monoamine oxidase substrates underlying adenosine antagonists inhibitors (MAOIs) impaired arousal 442--7 435--6 203--5 aging and sleep 443--5 mood stabilizers 436 thalamocortical arousal amphetamines 440--1 nicotine and sleep state dysfunction anesthetics 433--4 448--50 202--5 antidepressants and olanzapine 438, 439 see also dopamine sleep 435--8 orexins (hypocretins) PCPA (p-chloro- antipsychotic and sleep 450--1 phenylalanine), medications and ramelteon 435 effects of 31--2 sleep 438--40 reboxetine 437--8 perifornical hypothalamus, atypical antipsychotics risperidone 438 orexin (hypocretin) 440 serotonin reuptake neurons 38--9, barbiturates 433--4 inhibitors 435--6 95--6, 97 BenzedrineTM 440--1 trazodone 437 perifornical lateral benzodiazepines 433--5 tricyclic antidepressants hypothalamus (PLH) cAMP regulated (TCAs) 435--6 efferents from POA pathways 435--6 venlafaxine 437--8 sleep-active neurons CNS stimulants and zolpidem 434, 437--8 8, 9 sleep 440--50 zopiclone 434 GABAergic control of cocaine 440--1 pineal gland, biosynthesis orexin (hypocretin) cyclopyrrolones 434 and secretion of neurons 7, 10, 11, dopamine-acting drugs melatonin 283 12 440--1 plasticity related genes, neuronal projections dopaminergic D-1 and activation 33 from the MnPN 4 D-2 receptor PLH see perifornical lateral periodic leg movements of antagonists 439--40 hypothalamus sleep 179, 185 fluoxetine 437--8 POA see preoptic area

Index 477

pons, effects of glutamate effects of sleep neurochemical neurotransmission deprivation 125, regulatory 225--6 126 mechanisms 15--17 pontine cholinergic agonists, preoptic area (POA) phenotype 4, 5 effects on REM GABAergic neurons sleep–wake switch sleep 112--16 40--1 model 14 pontine region preoptic area (POA) studies of neuronal distinct nuclear groups hypnogenic system activity 6--8 62--3 hypnogenic mechanism see also sleep-active role in REM sleep 3 neurons generation role in homeostatic prostaglandin D (PGD) 61--3 control of sleep 15 receptors 370--2

pontine reticular formation thermosensitive CRTH2 (DP2) receptor ACh release during REM component 10--14 371

sleep 110, 113, preoptic area (POA) DP (DP1) receptor (DPR) 119--21, 122 sleep-active neurons 371--2 effects of glutamate 3 location of DPR neurotransmission actions of sedative receptors 371--2 225--6 hypnotic drugs 17 role of adenosine 372--4 pontis reticularis oralis c-Fos immunoreactivity prostaglandin D synthase (PRO), role in REM mapping 3--4 (L-PGDS/␤-trace) sleep generation effects of adenosine 364, 366--70 61--3 sleep factor ␤-trace biomarker posterior hypothalamus (PH) 16--17 368--9 GABA release during effects of IL-1␤ sleep genetic studies 369--70 sleep 7, 10, 11, factor 16 localization 368--9 12 effects of PGD2 sleep structure and function role in control of factor 17 364, 366--8

sleep–wake cycle efferents to arousal prostaglandin D2 (PGD2) and 157 systems 8, 9 sleep 364--72 role in PS onset and GABA synthesis 4, 5 involvement in African maintenance 95, GABAergic projections sleeping sickness 96--7 to arousal systems 366 PPT (pedunculopontine 8, 9 involvement in tegmentum), effects glutamic acid mastocytosis 366 of glutamate decarboxylase (GAD) PGD synthase genetic neurotransmission co-localization 4, studies 369--70 226 5 PGD synthase prefrontal cortex hypnogenic sleep factors localization 368--9 effects of anesthesia 15--17 PGD synthase structure 125, 126 in the MnPN 3--4, 5, 6 and function 364, effects of autoreceptor in the VLPO 3--4, 5, 6 366--8 modulation of ACh localization within the role of adenosine 372--4 125--9 POA 3--4, 6 sleep factor 17

478 Index

prostaglandin D2 (cont.) formation 110, 113, modulation by sleep-inducing activity 119--21, 122 urotensin II 394--5

of PGD2 364--6 and enhanced EEG reciprocal interaction TMN wake center 374--6 activity 109--11 model 34--6 VLPO sleep center brain electrical activity role of acetylcholine 374--6 60--1 27--8

prostaglandin E2 (PGE2) and brain regions species which show it wakefulness 364, controlling 24--6 60--1 376--7 causes of variation 61 variation with age 61 prostaglandins (PG) discovery in humans see also paradoxical sleep discovery of 364 25--6 (PS) range of organisms discovery of 60 REM sleep behaviour which have PGs effects in orexin- and disorder, in 366 orexin Parkinson’s disease structure and formation receptor-deﬁcient 202, 203, 205--6 364 rodents 415--16 REM sleep deprivation prostanoids, structure and effects of ACh esterase and hypothermia 71--3 formation 364 inhibitors 112--16 and increased food effects of ACh intake 71--3 ramelteon (RozeremTM) transporter effects of increased NA (melatonin agonist) blockade 110, 130, levels in the brain 300--1, 435 131 71--3 reboxetine 437--8 effects of autoreceptor mechanisms for adverse reciprocal interaction model modulation of ACh effects 71--3 of REM sleep 34--6, 110, 113, 121--9 patho-physiological 68--9 effects of blocking ACh effects 61 GABAergic inhibition of degradation 109--11 REM sleep disorders, and monoaminergic effects of choline dopamine activity neurons 91--4 transporter 179 integration of orexins blockade 110, REM sleep dysregulation, in (hypocretins) 129--30 orexin- and orexin 389--91 effects of diseases 61 receptor-deﬁcient REM sleep (paradoxical effects of rodents 415 sleep) onset and dopaminomimetics REM sleep generation maintenance 86--8 200 role of muscarinic recovery sleep, cause of effects of nicotine cholinergic 346--7 (cigarette smoke) receptors 115, REM muscle atonia, role of 131--2 116--18 glycine 43 effects of pontine role of the LC 61--3 REM-ON and REM-OFF cholinergic agonists role of the pontine neurons 34--6, 63 112--16 region 61--3 REM sleep (paradoxical sleep) functions 61 role of the pontis ACh release in the in mammals and birds reticularis oralis pontine reticular 60--1 61--3

Index 479

REM sleep regulatory afferent connections range of functions neurotransmitters 249, 250 256--7 63--70 efferent connections structure 29 acetylcholine 66 247--8, 249 synthesis and dopamine 65 rates of ﬁring in catabolism 29--30, GABA 66--8 sleep–wake 31 GABAergic Inhibition regulation 250--2 serotonin receptors see 5–HT Based Model 69--70, serotonergic median raphe receptors 71 neurons 247 serotonin reuptake histamine 65--6 afferent connections inhibitors 435--6 interactions between 249, 250 serotonin reuptake 68--70 efferent connection transporters (SERT) Mutual Inhibitory Model 247--8, 249 31 69 serotonergic raphe neurons sleep-active neurons noradrenaline 63--4 29--32 in the basal forebrain orexin (hypocretin) 68 activity levels 31--2 (BF) 6 Reciprocal Interaction auto- and in the hypothalamic Model 68--9 heteroreceptors POA 3 serotonin 65 32 see also preoptic area reptiles, brain electrical caudal group 247 (POA) sleep-active activity in rest state control of activity and neurons 60--1 serotonin release sleep-active warm-sensitive reserpine (from Rauwolfia 32 neurons (WSNs) vomitoria)33 distribution 31 in the POA 10--14 restless legs syndrome 179, rostral group 247 inhibition of arousal 185 serotonin (5-hydroxy- systems 13, 14 reverse genetics, use in the tryptamine, 5-HT) sleep and wakefulness study of and PGO spikes 32 electrophysiological neuropeptides and REM sleep correlates 60--1 388--9, 392, 396 regulation 65 variations in the state of risperidone 438 changing view of role in consciousness sleep–wake 60--1 schizophrenia, sleep regulation 246--7 see also sleep–wake disturbances discovery 29 regulation 438--40 discovery of sleep deprivation sedative hypnotic drugs, neurotransmitter and energy imbalance actions 17 function 29 346--7 selective serotonin reuptake effects on sleep 31--2 cause of recovery sleep inhibitors (SSRIs) enhancement of 346--7 31 extracellular levels cause of rise in

effects on 5-HT1A 31 adenosine 346--7 receptor 259--60 monoaminergic theory effects of energy serotonergic dorsal raphe of sleep and waking imbalance 346--7 neurons 247 31--2 effects of NO 346--7

480 Index

sleep deprivation (cont.) orexin–ghrelin–NPY treatment of age-related source of increased circuit 318--22, 323 circadian changes adenosine 345--6 scope of search for 294 vulnerability of the 317--18 treatment of circadian prefrontal cortex tumor necrosis factor ␣ rhythm problems in 125, 126 (TNF␣)316 blind people 294 sleep disorder treatments see also adenosine; treatment of delayed (serotonin-related) hypnogenic sleep sleep phase 31 factors syndrome 294 sleep disorders sleep factors, history of treatment of jet lag adenosine applications attempts to isolate a symptoms 293--4 352--3 sleep factor from treatment of sleep melatonin treatment animals 315--17 disorders 291--4 291--4 delta-sleep-inducing wake-maintenance zone periodic leg movement peptide (DSIP) (‘forbidden zone’) 179 316--17 291 potential use of historical search for the sleep-onset REM periods glutamate receptor ‘hypnotoxin’ (SOREMs), in agonists/antagonists 315--17 Parkinson’s disease 239--40 muramyl peptides 202--5 REM sleep disorders (Factor S) 315--16 sleep paralysis 405, 406 179 search for a key sleep propensity, and body restless legs syndrome endogenous temperature 10--14 179 substance 315--17 sleep regulation see sleep treatment with search for a key factors; sleep–wake melatonin agonists hormone 315--16 regulation 299--301 somnogenic action of sleep switch (flip–flop) model sleep factors cytokines 316 40, 41--2 criteria for 337--8 SPS-A and SPS-B 317 interaction of orexin cytokines 316 sleep modulation by (hypocretin) and definition 328--9 melatonin (human) MCH 426 early research 337--8 290--1 proposed role of orexin ghrelin 318--21, 322, circadian phase-shifting (hypocretin) 323 effects of melatonin neurons 391 interferon alpha 2 316 293--4 role of neuropeptide S interleukin 1 (IL-1) 316 effects of endogenous (NPS) 395--6, 397 neuropeptide Y (NPY) melatonin role of POA sleep-active 319, 321--2, 323 administration neurons 14 neurotransmitters and 291--4 sleep–wake regulation neuromodulators neuropharmacological Borbély’s two-process 317--18 mechanisms theory 337 nitric oxide (NO) 322--8 295--9, 300 changing view of role of obestatin 321 opening of the sleep serotonin (5-HT) orexin 318, 322, 323 gate 290--1 246--7

Index 481

circadian process 337 sleep–wake regulatory effects of glutamate criteria for sleep factors neurons, rates of neurotransmission 337--8 firing 250--2 227--8 early research 337--8 sleep–wake stages, theophylline, adenosine effects of glutamate neurotransmitter receptor targets 45 neurotransmission systems involved thermoregulation, and sleep 225--8 433 10--14 homeostatic process slow wave sleep, effects of TMN see tuberomammillary 337, 338 cortistatin 392--4 nucleus humoral theory 363 smoking, effects on sleep trazodone 437 influence of energy 131--2 tricyclic antidepressants balance 424--7 soluflazine 340 (TCAs) 435--6 interaction of orexin somatostatin 392 tuberohypophyseal and MCH 424--7 somatostatin receptors dopamine pathway neural structures 392 184--5 involved 244--6 state-related dysfunction, in tuberoinfundibular neurotransmitters Parkinson’s disease dopamine pathway involved 244--6 202--6 184--5

role of 5-HT1A receptor stimulants, adenosine tuberomammillary nucleus 257--60 receptor targets 45 (TMN), effects of

role of 5-HT1B receptor sublaterodorsal nucleus PGD2 374--6 260 (SLD), role in tuberomammillary nucleus

role of 5-HT2A/2B/2C paradoxical sleep (TMN) histaminergic receptors 261--3 88--91 neurons 36--8,

role of 5-HT3 receptor subparafascicular thalamus, 147--8 263--4 dopamine cell action of histamine on

role of 5-HT7 receptor group 185 151 264--5 suprachiasmatic nucleus action of role of cortistatin 392--4 actions of NO neurotransmitters role of neuropeptide S 327--8 and (NPS) 395--6, 397 control of melatonin neuromodulators role of orexins secretion 285--6 on 151--3 (hypocretins) effects of glutamate activity during 388--91 neurotransmission wakefulness 145 role of the lateral 226 activity levels 37--8 hypothalamus (LH) synaptic plasticity, afferents to 150 424--6 promotion of 34 dopaminergic inputs role of urotensin II 150 394--5 thalamocortical arousal state efferent projections in search for endogenous dysfunction, in the CNS 148--9 somnogenic Parkinson’s disease GABAergic inputs 150 substances 363 202--5 galanin inputs 150 search for sleep factors thalamus localization in the TMN 337--8 acetylcholine release 27 37

482 Index

tuberomammillary nucleus effects of prostaglandin wake–sleep regulation see

(TMN) (cont.) D2 (PGD2) 374--6 sleep–wake method of release of efferents to arousal regulation histamine 37 systems 8 wake–sleep transitions see orexinergic inputs 150 GABAergic neurons sleep switch physiology 150--1 40--1 (flip–flop) model tumor necrosis factor ␣ sleep-active neurons wakefulness (TNF␣), as a sleep 3--4, 5, 6 activity of factor 316 vesicular ACh transporter monoaminergic blockade, effects on systems 145 urotensin II REM sleep 110, 130, brain regions and sleep–wake 131 controlling regulation 394--5 vigilance states, effects of 24--6 effect on peripheral orexin deficiency cortical activation by vasculature 394--5 422--4 neurotransmitters modulation of REM VLPO see ventrolateral POA 145 sleep 394--5 voltammetry 23--4 EEG activity 145 warm-sensitive neurons valproic acid 289--90 wake-maintenance zone (WSNs) in the POA venlafaxine 437--8 (‘‘forbidden zone”) 10--14 ventrolateral POA (VLPO) 291

case for A2AR-mediated wake-promoting neuronal zolpidem 434, action in 349, groups, studies of 437--8 350--2 neuronal activity 8 zopiclone 434