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Neuronal Networks Regulating Sleep and Arousal: Effect of Drugs

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Drug Treatment of Sleep Disorders

Part of the book series: Milestones in Drug Therapy ((MDT))

Abstract

The three vigilance states (wakefulness [W], slow wave sleep [SWS], rapid eye movement sleep [REMS]) are controlled by distinct, but interconnected, networks of neurons. The sleep/arousal network consists of separate systems of W-promoting and SWS-promoting neurons, located in nuclei in the basal forebrain, diencephalon and brainstem. Each neuronal system operates via a distinct neurotransmitter, providing its unique “neurochemical signature”. W-promoting neurons are active during W and quiescent during SWS, whereas SWS-promoting neurons are active during SWS and cease to fire during W. The level of arousal at any one time reflects the intricate balance between W-promoting and SWS-promoting systems. W is the result of cortical activation by W-promoting neurons; sleep ensues when SWS-promoting neurons switch off the W-promoting systems. REMS is regulated by a network of REMS-promoting and REMS-inhibiting neurons located in the brainstem and hypothalamus. A third network is responsible for the regulation of the circadian rhythmicity of the wakefulness/sleep cycle. The neurochemical signatures of W-promoting and SWS-promoting neurons make it possible to develop drugs that, by targeting specific neuroreceptors and synaptic mechanisms, have predictable effects on sleep and arousal. Arousal-modifying drugs act by tipping the balance between W-promoting and SWS-promoting neuronal activity. Thus a sedative drug, useful for the treatment of insomnia, may act by activating a SWS-promoting system (e.g. benzodiazepines, melatonin receptor agonists) or inhibiting a W-promoting system (e.g. H1-antihistamines, orexin receptor antagonists). Conversely, an alerting drug, useful for the treatment of excessive daytime sleepiness, may inhibit a SWS-promoting system or activate a W-promoting system (e.g. psychostimulants, H3 histamine receptor antagonists).

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Abbreviations

BF:

Basal forebrain

DMH:

Dorsomedial hypothalamus

DR:

Dorsal raphe nucleus

LC:

Locus coeruleus

LDT:

Laterodorsal tegmental nucleus

LGN:

Lateral geniculate nucleus

LH:

Lateral hypothalamic area

MCH:

Melanin concentrating hormone

PBN:

Parabrachial nucleus

PC:

Precoeruleus nucleus

PF:

Perifornical area

PPT:

Pedunculopontine tegmental nucleus

PVN:

Paraventricular nucleus

SCN:

Suprachiasmatic nucleus

SLD:

Sublaterodorsal nucleus

SPZ:

Subparaventricular zone

Th:

Thalamus

TMN:

Tuberomamillary nucleus

TPR:

Tegmentopontine reticular nucleus

vGC:

Ventral gigantocellular nucleus

vlPAG:

Ventrolateral periaquductal grey (matter)

VLPO:

Ventrolateral preopic nucleus

VPAG:

Ventral periaquductal grey (matter)

VTA:

Ventral tegmental area

References

  • Abe Y, Aoyagi A, Hara T et al (2003) Pharmacological characterization of RS-1259, an orally active dual inhibitor of acetylcholinesterase and serotonin transporter, in rodents: possible treatment of Alzheimer’s disease. J Pharmacol Sci 93:95–105

    CAS  PubMed  Google Scholar 

  • Abercrombie ED, Jacobs BL (1987) Microinjected clonidine inhibits noradrenergic neurons of the locus coeruleus in freely moving cats. Neurosci Lett 76:203–208

    CAS  PubMed  Google Scholar 

  • Ahnaou A, Drinkenburg WHIM, Bouwknecht JA et al (2008) Blocking melanin-concentrating hormone MCH1 receptor affects rat sleep-wake architecture. Eur J Pharmacol 579:177–188

    CAS  PubMed  Google Scholar 

  • Ahnaou A, Dautzenberg FM, Geys H et al (2009) Modulation of group II metabotropic glutamate receptor (mGlu2) elecits common changes in rat and mice sleep-wake architecture. Eur J Pharmacol 603:62–72

    CAS  PubMed  Google Scholar 

  • Ahnaou A, Ver Donck L, Drinkenburg WHIM (2014) Blockade of the metabotropic glutamate (mGluR2) modulates arousal through vigilance states transitions: evidence from sleep-wake EEG in rodents. Behav Brain Res 270:56–67

    CAS  PubMed  Google Scholar 

  • Argiolas A, Melis MR (2005) Central control of penile erection: role of the paraventricular nucleus of the hypothalamus. Prog Neurobiol 76:1–21

    CAS  PubMed  Google Scholar 

  • Arias-Carrión O, Murillo-Rodriguez E (2014) Effects of hypocretin/orexin cell transplantation on narcoleptic-like sleep behavior in rats. PLoS One 9:e95342

    PubMed Central  PubMed  Google Scholar 

  • Arrang JM, Morisset S, Gbahou F (2007) Constitutive activity of the histamine H3 receptor. Trends Pharmacol Sci 28:350–357

    CAS  PubMed  Google Scholar 

  • Aston-Jones G (2005) Brain structures and receptors involved in alertness. Sleep Med 6(Suppl 1):S3–S7

    PubMed  Google Scholar 

  • Aston-Jones G, Cohen JD (2005) An integrative theory of locus coeruleus-norepinephrine function: adaptive gain and optimal performance. Annu Rev Neurosci 28:403–450

    CAS  PubMed  Google Scholar 

  • Atack JR (2010) Preclinical and clinical pharmacology of the GABAA receptor α5 subtype inverse agonist α5IA. Pharmacol Ther 125:11–26

    CAS  PubMed  Google Scholar 

  • Bay T, Eghorn L, Klein AB et al (2014) GHB receptor targets in the CNS: focus on high-affinity binding sites. Biochem Pharmacol 87:220–228

    CAS  PubMed  Google Scholar 

  • Beaulieu J-M, Gainetdinov RR (2011) The physiology, signaling, and pharmacology of dopamine receptors. Pharmacol Rev 63:182–217

    CAS  PubMed  Google Scholar 

  • Belelli D, Peden DR, Rosahl TW et al (2005) Extrasynaptic GABAA receptors of thalamocortical neurons: a molecular target for hypnotics. J Neurosci 25:11513–11520

    CAS  PubMed  Google Scholar 

  • Benington JH, Kodali SK, Heller HC et al (1995) Stimulation of A1 adenosine receptors mimics the electroencephalographic effects of sleep deprivation. Brain Res 692:79–85

    CAS  PubMed  Google Scholar 

  • Berigan TR (2002) Modafinil treatment of excessive daytime sedation and fatigue associated with topiramate. Prim Care Companion J Clin Psychiatry 4:249–250

    PubMed Central  PubMed  Google Scholar 

  • Berlin M, Boyce CW, Ruiz Mde L (2011) Histamine H3 receptor as a drug discovery target. J Med Chem 54:26–53

    CAS  PubMed  Google Scholar 

  • Bien CG, Vincent A, Barnett MH et al (2012) Immunopathology of autoantibody-associated encephalitides: clues for pathogenesis. Brain 135:1622–1638

    PubMed  Google Scholar 

  • Boscolo-Berto R, Viel G, Montagnese S et al (2012) Narcolepsy and effectiveness of gamma-hydroxybutyrate (GHB): a systematic review and meta-analysis of randomized controlled trials. Sleep Med Rev 16:431–443

    PubMed  Google Scholar 

  • Bowery NG (2006) GABAB receptor: a site of therapeutic benefit. Curr Opin Pharmacol 6:37–43

    CAS  PubMed  Google Scholar 

  • Brioni JD, Esbenshade TA, Garrison TR et al (2011) Discovery of histamine H3 antagonists for the treatment of cognitive disorders and Alzheimer’s disease. J Pharmacol Exp Ther 336:38–46

    CAS  PubMed  Google Scholar 

  • Brown DA (2010) Muscarinic acetylcholine receptors (mAChRs) in the nervous system: some functions and mechanisms. J Mol Neurosci 41:340–346

    CAS  PubMed  Google Scholar 

  • Brown RE, Basheer R, McKenna JT et al (2012) Control of sleep and wakefulness. Physiol Rev 92:1087–1187

    CAS  PubMed Central  PubMed  Google Scholar 

  • Bubser M, Fadel JR, Jackson LL et al (2005) Dopaminergic regulation of orexin neurons. Eur J Neurosci 21:2993–3001

    PubMed  Google Scholar 

  • Büttner-Ennever JA, Horn AKE (1997) Anatomical substrates of oculomotor control. Curr Opin Neurobiol 7:872879

    Google Scholar 

  • Carter ME, Yizhar O, Chikahisha S et al (2010) Tuning arousal with optogenetic modulation of locus coeruleus neurons. Nat Neurosci 13:1526–1533

    CAS  PubMed Central  PubMed  Google Scholar 

  • Cavas M, Scesa G, Navarro JF (2013a) Effects of MPEP, a selective metabotropic glutamate mGlu5 ligand, on sleep and wakefulness in the rat. Prog Neuropsychopharmacol Biol Psychiatry 40:18–25

    CAS  PubMed  Google Scholar 

  • Cavas M, Scesa G, Navarro JF (2013b) Positive allosteric modulation of mGlu7 receptors by AMN082 affects sleep and wakefulness in the rat. Pharmacol Biochem Behav 103:756–763

    CAS  PubMed  Google Scholar 

  • Chase MH (2013) Motor control during sleep and wakefulness: clarifying controversies and resolving paradoxes. Sleep Med Rev 17:299–312

    PubMed  Google Scholar 

  • Christie MJ (1991) Mechanisms of opioid actions on neurons of the locus coeruleus. Prog Brain Res 88:197–20

    CAS  PubMed  Google Scholar 

  • Church MK, Church DS (2013) Pharmacology of antihistamines. Indian J Dermatol 58:219–224

    PubMed Central  PubMed  Google Scholar 

  • Cicolin A, Magliola U, Giordano A et al (2006) Effects of levetiracetam on nocturnal sleep and daytime vigilance in healthy volunteers. Epilepsia 47:82–85

    CAS  PubMed  Google Scholar 

  • Cronin A, Keier JC, Baghdoyan HA et al (1995) Opioid inhibition of rapid eye movement sleep by a specific mu receptor agonist. Br J Anaesth 74:188–192

    CAS  PubMed  Google Scholar 

  • Datta S, McLean RR (2007) Neurobiological mechanisms for the regulation of mammalian sleep-wake behavior: reinterpretation of historical evidence and inclusion of contemporary cellular molecular evidence. Neurosci Biobehav Rev 31:775–824

    CAS  PubMed Central  PubMed  Google Scholar 

  • Deutch AY, Goldstein M, Roth RH (1986) Activation of the locus coeruleus induced by selective stimulation of the ventral tegmental area. Brain Res 363:307–314

    CAS  PubMed  Google Scholar 

  • Dijk DJ, Brunner DP, Aeschbach D et al (1992) The effects of ethanol on human sleep EEG power spectra differ from those of benzodiazepine receptor agonists. Neuropsychopharmacology 7:225–232

    CAS  PubMed  Google Scholar 

  • Dingledine R, Borges K, Bowie D et al (1999) The glutamate receptor ion channels. Pharmacol Rev 51:7–61

    CAS  PubMed  Google Scholar 

  • Dodson ER, Zee PC (2010) Therapeutics for circadian rhythm sleep disorders. Sleep Med Clin 5:701–771

    PubMed Central  PubMed  Google Scholar 

  • Dunbar G, Boeijinga PH, Demazières A et al (2007) Effects of TC-1734 (AZD3480), a selective neuronal nicotinic receptor agonist, on cognitive performance and the EEG of young healthy male volunteers. Psychopharmacology 191:919–929

    CAS  PubMed  Google Scholar 

  • Ebert U, Kirch W (1998) Scopolamine model of dementia: electroencephalogram findings and cognitive performance. Eur J Clin Invest 28:944–949

    CAS  PubMed  Google Scholar 

  • España RA, Scammell TE (2011) Sleep neurobiology from a clinical perspective. Sleep 34:845–858

    PubMed Central  PubMed  Google Scholar 

  • Esplin DW (1970) Drugs acting on the central nervous system – introduction. In: Goodman LS, Gilman A (eds) The pharmacological basis of therapeutics, 4th edn. Macmillan, New York, pp 36–42

    Google Scholar 

  • Fares A (2011) Night-time exogenous melatonin administration may be a beneficial treatment for sleeping disorders in beta blocker patients. J Cardiovasc Dis Res 2:153–155

    CAS  PubMed Central  PubMed  Google Scholar 

  • Fisher DJ, Daniels R, Jaworska N et al (2012) Effects of acute nicotine administration on resting EEG in nonsmokers. Exp Clin Psychopharmacol 20:71–75

    CAS  PubMed  Google Scholar 

  • Fort P, Bassetti CL, Luppi PH (2009) Alternating vigilance states: new insights regarding neuronal networks and mechanisms. Eur J Neurosci 29:1741–1753

    CAS  PubMed  Google Scholar 

  • Freeman A, Ciliax B, Bakay R et al (2001) Nigrostriatal collaterals to thalamus degenerate in parkinsonian animal models. Ann Neurol 50:321–329

    CAS  PubMed  Google Scholar 

  • Frisullo G, Della Marca G, Mirabella M (2007) A human anti-neuronal autoantibody against GABAB receptor induces experimental autoimmune agrypnia. Exp Neurol 204:808–818

    CAS  PubMed  Google Scholar 

  • Froestl W, Gallagher M, Jenkins H et al (2004) SGS742: the first GABAB receptor antagonist in clinical trials. Biochem Pharmacol 68:1479–1478

    CAS  PubMed  Google Scholar 

  • Fuller PM, Gooley JJ, Saper CB (2006) Neurobiology of the sleep-wake cycle: sleep architecture, circadian regulation, and regulatory feedback. J Biol Rhythms 21:482–493

    CAS  PubMed  Google Scholar 

  • Fuller P, Sherman D, Pedersen NP et al (2011) Reassessment of the structural basis of the ascending arousal system. J Comp Neurol 519:933–956

    PubMed Central  PubMed  Google Scholar 

  • Gallopin T, Luppi PH, Cauli B et al (2005) The endogeneous somnogen adenosine excites a subset of sleep-promoting neurons via A2A receptors in the ventrolateral preoptic nucleus. Neuroscience 134:1377–1390

    CAS  PubMed  Google Scholar 

  • Gaus SE, Strecker E, Tate BA et al (2002) Ventrolateral preoptic nucleus contains sleep-active, galaninergic neurons in multiple mammalian species. Neuroscience 115:285–294

    CAS  PubMed  Google Scholar 

  • Gemkow MJ, Davenport AJ, Harich S et al (2009) The histamine H3 receptor as a therapeutic target for CNS disorders. Drug Discov Today 14:9–10

    Google Scholar 

  • Gitto R, De Luca L, De Grazia S et al (2012) Glutamatergic neurotransmission as molecular target of new anticonvulsants. Curr Top Med Chem 12:971–993

    CAS  PubMed  Google Scholar 

  • Giuliano F, Rampin O (2004) Neural control of erection. Physiol Behav 83:189–201

    CAS  PubMed  Google Scholar 

  • Glue P, Wilson S, Lawson C (1991) Acute and chronic idazoxan in normal volunteers: biochemical, physiological and psychological effects. J Psychopharmacol 5:396–403

    CAS  PubMed  Google Scholar 

  • Gobert A, Rivet J-M, Lejeune F et al (2000) Serotonin2C receptors tonically suppress the activity of mesocortical dopaminergic and adrenergic, but not serotonergic, pathways: a combined dialysis and electrophysiological analysis in the rat. Synapse 36:205–221

    CAS  PubMed  Google Scholar 

  • Göder R, Seeck-Hirschner M, Stingele K (2011) Sleep and cognition at baseline and the effects of REM sleep diminution after 1 week of antidepressive treatment in patients with depression. J Sleep Res 20:544–551

    PubMed  Google Scholar 

  • Gottesmann C (2002) GABA mechanisms and sleep. Neuroscience 111:231–239

    CAS  PubMed  Google Scholar 

  • Gottesmann C (2011) The involvement of noradrenaline in rapid eye movement sleep mentation. Front Neurol 2:1–10 (Article 81)

    Google Scholar 

  • Gotti C, Clementi F, Fornari A et al (2009) Structural and functional diversity of native brain neuronal nicotinic receptors. Biochem Pharmacol 78:703–711

    CAS  PubMed  Google Scholar 

  • Haas HL, Lin J-S (2012) Waking with the hypothalamus. Pflugers Arch Eur J Physiol 463:31–42

    CAS  Google Scholar 

  • Hardeland R (2012) Melatonin in aging and disease – multiple consequences of reduced secretion, options and limits of treatment. Aging Dis 3:194–225

    PubMed Central  PubMed  Google Scholar 

  • Hassani OK, Lee MG, Jones BE (2009) Melanin-concentrating hormone neurons discharge in a reciprocal manner to orexin neurons across the sleep-wake cycle. Proc Natl Acad Sci USA 106:2418–2422

    CAS  PubMed Central  PubMed  Google Scholar 

  • Heinzer RC, Sériès F (2011) Normal physiology of the upper and lower airways. In: Kryger MH, Roth T, Dement WS (eds) Principles and practice of sleep medicine, 5th edn. Elsevier, St Louis, pp 259–268

    Google Scholar 

  • Hirshkowitz M, Schmidt MH (2005) Sleep-related erections: clinical perspectives and neural mechanisms. Sleep Med Rev 9:311–329

    PubMed  Google Scholar 

  • Hobson JA (2009) REM sleep and dreaming: towards a theory of protoconsciousness. Nat Rev Neurosci 10:803–813

    CAS  PubMed  Google Scholar 

  • Hoffman EJ, Warren EW (1993) Flumazenil: a benzodiazepine antagonist. Clin Pharm 12:641–656

    CAS  PubMed  Google Scholar 

  • Hossmann V, Maling TJ, Hamilton CA et al (1980) Sedative and cardiovascular effects of clonidine and nitrazepam. Clin Pharmacol Ther 28:167–176

    CAS  PubMed  Google Scholar 

  • Hoyer D (2010) Neuropeptide receptor positive allosteric modulation in epilepsy: galanin modulation revealed. Proc Natl Acad Sci USA 107:14943–1494

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hoyer D, Jacobson LH (2013) Orexin in sleep, addiction and more: is the perfect insomnia drug at hand? Neuropeptides 47:477–488

    CAS  PubMed  Google Scholar 

  • Hoyer D, Hannon JP, Martin GR (2002) Molecular, pharmacological and functional diversity of 5-HT receptors. Pharmacol Biochem Behav 71:533–554

    CAS  PubMed  Google Scholar 

  • Huang Z-L, Qu W-M, Eguchi N (2005) Adenosine A2A, but not A1, receptors mediate the arousal effect of caffeine. Nat Neurosci 8:858–859

    CAS  PubMed  Google Scholar 

  • Huang Z-L, Urade Y, Hayaishi O (2011) The role of adenosine in the regulation of sleep. Curr Top Med Chem 11:1047–1057

    CAS  PubMed  Google Scholar 

  • Huang H-P, Zhu F-P, Chen X-W et al (2012) Physiology of quantal norepinephrine release from somatodendritic sites of neurons in locus coeruleus. Front Mol Neurosci 5:1–5 (Article 29)

    Google Scholar 

  • Jego S, Glasgow SD, Gutierrez Herrera C et al (2013) Optogenetic identification of a rapid eye movement sleep modulatory circuit in the hypothalamus. Nat Neurosci 16:1637–1643

    CAS  PubMed  Google Scholar 

  • Johnson EO, Roehrs T, Roth T et al (1998) Epidemiology of alcohol and medication as aids to sleep in early adulthood. Sleep 21:178–186

    CAS  PubMed  Google Scholar 

  • Johnston GAR (2013) Advantages of an antagonist: bicuculline and other GABA antagonists. Br J Pharmacol 169:328–336

    CAS  PubMed Central  PubMed  Google Scholar 

  • Johnston GA, Chebib M, Hanrahan JR et al (2003) GABA(C) receptors as drug targets. Curr Drug Targets CNS Neurol Disord 2:260–268

    CAS  PubMed  Google Scholar 

  • Kalsbeek A, Garidou ML, Palm IF et al (2000) Melatonin sees the light: blocking GABA-ergic transmission in the paraventricular nucleus induces daytime secretion of melatonin. Eur J Neurosci 12:3146–3154

    CAS  PubMed  Google Scholar 

  • Kalsbeek A, Palm IF, La Fleur SE et al (2006) SCN outputs and the hypothalamic balance of life. J Biol Rhythms 21:458–469

    CAS  PubMed  Google Scholar 

  • Keating GL, Rye DB (2003) Where you least expect it: dopamine in the pons and modulation of sleep and REM-sleep. Sleep 26:788–789

    PubMed  Google Scholar 

  • Kenney C, Jankoovic J (2006) Tetrabenazine in the treatment of hyperkinetic movement disorders. Mov Disord 22:193–197

    Google Scholar 

  • Ko EM, Eastbrooke IV, McCarthy M et al (2003) Wake-related activity of tubermammillary neurons in rats. Brain Res 992:220–226

    CAS  PubMed  Google Scholar 

  • Kohlmeier KA, Vardar B, Christensen MH (2013) γ-Hydroxybutyric acid induces actions via the GABAB receptor in arousal and motor control-related nuclei: implication for therapeutic actions in behavioural state disorders. Neuroscience 248:261–277

    CAS  PubMed  Google Scholar 

  • Kratochvil CJ, Vaughan BS, Harrington MJ et al (2003) Atomoxetine: a selective noradrenaline reuptake inhibitor for the treatment of attention-deficit/hyperactivity disorder. Expert Opin Pharmacother 4:1165–1174

    CAS  PubMed  Google Scholar 

  • Krenzer M, Anaclet C, Vetrivelan R et al (2011) Brainstem and spinal cord circuitry regulating REM sleep and muscle atonia. PLoS One 6(10):e24998

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kulisevsky J, Poyurovsky M (2012) Adenosine A2A-receptor antagonism and pathophysiology of Parkinson’s disease and drug-induced movement disorders. Eur Neurol 67:4–11

    CAS  PubMed  Google Scholar 

  • Lal H, Kumar B, Forster MJ (1988) Enhancement of learning and memory in mice by a benzodiazepine antagonist. FASEB J 2:2707–2711

    CAS  PubMed  Google Scholar 

  • Lambert JL, Cooper MA, Simmons RDJ et al (2009) Neurosteroids: endogenous allosteric modulators of GABAA receptors. Psychoneuroendocrinology 34S:S48–S58

    Google Scholar 

  • Lancaster E, Lai M, Peng X et al (2010) Antibodies to the GABAB receptor in limbic encephalitis with seizures: case series and characterisation of antigen. Lancet Neurol 9:67–76

    CAS  PubMed Central  PubMed  Google Scholar 

  • Landolt H-P (2008) Sleep homeostasis: a role for adenosine in humans? Biochem Pharmacol 75:2070–2079

    CAS  PubMed  Google Scholar 

  • Lane SD, Green CE, Steinberg JL et al (2012) Cardiovascular and subjective effects of the novel adenosine A2A receptor antagonist SYN115 in cocaine dependent individuals. J Addict Res Ther Suppl 1:1–15

    Google Scholar 

  • Lazarus M, Shen H-Y, Cherasse Y et al (2011) Arousal effect of caffeine depends on adenosine A2A receptors in the shell of the nucleus accumbens. J Neurosci 31:10067–10075

    CAS  PubMed Central  PubMed  Google Scholar 

  • Le Maître E, Barde SS, Palkovits M et al (2013) Distinct features of neurotransmitter systems in the brain with focus on the galanin system in locus coeruleus and dorsal raphe. Proc Natl Acad Sci USA 110:E536–545

    PubMed Central  PubMed  Google Scholar 

  • Lee C-Y, Chen C-C, Liou H-H (2009) Levetiracetam inhibits glutamate transmission through presynaptic P/Q-type calcium channels on the granule cells of the dentate gyrus. Br J Pharmacol 158:1753–1762

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lerner JT, Sankar R, Mazarati AM (2008) Galanin and epilepsy. Cell Mol Life Sci 65:1864–1871

    CAS  PubMed  Google Scholar 

  • Leurs R, Blanidan P, Tedford C (1998) Therapeutic potential of histamine H3 receptor agonists and antagonists. Trends Pharmacol Sci 19:177–183

    CAS  PubMed  Google Scholar 

  • Lewis KS, Han NH (1997) Tramadol: a new centrally acting analgesic. Am J Health Syst Pharm 54:643–652

    CAS  PubMed  Google Scholar 

  • Lin JS, Sakai K, Jouvet M (1988) Evidence for histaminergic arousal mechanisms in the hypothalamus of cat. Neuropharmacology 27:111–122

    CAS  PubMed  Google Scholar 

  • Lin J-S, Anaclet C, Sergeeva OA et al (2011) The waking brain: an update. Cell Mol Life Sci 68:2499–2512

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lo YL, Jordan AS, Malhorra A et al (2007) The influence of wakefulness on pharyngeal muscle activity. Thorax 62:799–805

    PubMed Central  PubMed  Google Scholar 

  • Lu J, Shiromani P, Saper CB (1999) Retinal input to the sleep-active ventrolateral preoptic nucleus in the rat. Neuroscience 93:209–214

    CAS  PubMed  Google Scholar 

  • Lu J, Jhou TC, Saper CB (2006) Identification of wake-active dopaminergic neurons in the ventral periaqueductal gray matter. J Neurosci 26:193–202

    CAS  PubMed  Google Scholar 

  • Luppi P-H, Clément O, Sapin E et al (2011) The neuronal network responsible for paradoxical sleep and its dysfunctions causing narcolepsy and rapid eye movement (REM) behavior disorder. Sleep Med Rev 15:153–163

    PubMed  Google Scholar 

  • Luppi P-H, Clément O, Fort P (2013) Paradoxical (REM) sleep genesis by the brainstem is under hypothalamic control. Curr Opin Neurobiol 23:786–792

    CAS  PubMed  Google Scholar 

  • Lydic R, Baghdoyan HA (2007) Neurochemical mechanisms mediating opioid-induced REM sleep disruption. In: Lavigne G, Sessle B, Choinière M et al (eds) Sleep and pain. IASP Press, Seattle, pp 99–122

    Google Scholar 

  • Mandela P, Ordway GA (2006) The norepinephrine transporter and its regulation. J Neurochem 97:310–333

    CAS  PubMed  Google Scholar 

  • Manford M, Andermann F (1998) Complex visual hallucinations – clinical and neurobiological insights. Brain 121:1819–1840

    PubMed  Google Scholar 

  • Manfredi RL, Kales A, Vgontzas AN et al (1991) Buspirone: sedative or stimulant effect? Am J Psychiatry 148:1213–1217

    CAS  PubMed  Google Scholar 

  • Manns ID, Lee MG, Modirrousta M et al (2003) Alpha 2 adrenergic receptors on GABAergic, putative sleep-promoting basal forebrain neurons. Eur J Neurosci 18:723–727

    PubMed  Google Scholar 

  • Martinez-Cué C, Delatour B, Potier M-C (2014) Treating enhanced GABAergic inhibition in Down syndrome: use of GABA α5-selective inverse agonists. Neurosci Biobehav Rev. doi:10.1016/j.neurobiorev.2013.12.008

    PubMed  Google Scholar 

  • Massotti M, Lucantoni D, Caporali MG et al (1985) Supraspinal convulsions induced by inverse benzodiazepine agonists in rabbits. J Pharmacol Exp Ther 234:274–279

    CAS  PubMed  Google Scholar 

  • Matthias S, Wetter TC, Steiger A et al (2001) The GABA uptake inhibitor tiagabine promotes slow wave sleep in normal elderly subjects. Neurobiol Aging 22:247–253

    Google Scholar 

  • Max MB, Schafer SC, Culnane M et al (1988) Association of pain relief with drug side effects in postherpetic neuralgia: a single-dose study of clonidine, codeine, ibuprofen, and placebo. Clin Pharmacol Ther 43:363–371

    CAS  PubMed  Google Scholar 

  • McCarley RW (2007) Neurobiology of REM and NREM sleep. Sleep Med 8:302–330

    PubMed  Google Scholar 

  • McCormick DA (1992) Neurotransmitter actions in the thalamus and cerebral cortex and their role in neuromodulation of thalamocortical activity. Prog Neurobiol 39:37–388

    Google Scholar 

  • McCormick DA, Bal T (1997) Sleep and arousal: thalamocortical mechanisms. Annu Rev Neurosci 20:185–215

    CAS  PubMed  Google Scholar 

  • McGregor R, Siegel JM (2010) Illuminating the locus coeruleus: control of posture and arousal. Nat Neurosci 13:1448–1449

    CAS  PubMed  Google Scholar 

  • Meuret P, Backman SB, Bonhomme V et al (2000) Physostigmine reverses propofol-induced unconsciousness and attenuation of the auditory steady state response and bispectral index in human volunteers. Anesthesiology 93:708–717

    CAS  PubMed  Google Scholar 

  • Mieda M, Willie JT, Hara J et al (2004) Orexin peptides prevent cataplexy and improve wakefulness in an orexin neuron-ablated model of narcolepsy in mice. Proc Natl Acad Sci USA 101:4649–4654

    CAS  PubMed Central  PubMed  Google Scholar 

  • Minzenberg MJ, Watrous AJ, Yoon JH et al (2008) Modafinil shifts human locus coeruleus to low-tonic, high-phasic activity during functional MRI. Science 322:1700–1702

    CAS  PubMed  Google Scholar 

  • Mistlberger RE (2005) Circadian regulation of sleep in mammals: role of the suprachiasmatic nucleus. Brain Res Rev 49:429–454

    PubMed  Google Scholar 

  • Monti JM (2010) The structure of the dorsal raphe nucleus and its relevance to the regulation of sleep and wakefulness. Sleep Med Rev 14:307–317

    PubMed  Google Scholar 

  • Monti JM (2011) Serotonin control of sleep-wake behavior. Sleep Med Rev 15:269–281

    PubMed  Google Scholar 

  • Monti JM, Monti D (2007) The involvement of dopamine in the modulation of sleep and waking. Sleep Med Rev 11:113–133

    PubMed  Google Scholar 

  • Monti JM, Torterolo P, Lagos P (2013) Melanin-concentrating hormone control of sleep-wake behaviour. Sleep Med Rev 17:293–298

    PubMed  Google Scholar 

  • Moos DD (2007) Central anticholinergic syndrome: a case report. J Perianesth Nurs 22:309–321

    PubMed  Google Scholar 

  • Morairty S, Rainnie D, McCarley R et al (2004) Disinhibition of ventrolateral preoptic area sleep-active neurons by adenosine: a new mechanism for sleep promotion. Neuroscience 123:451–457

    CAS  PubMed  Google Scholar 

  • Müller U, Rowe JB, Rittman T et al (2013) Effects of modafinil on non-verbal cognition, task enjoyment and creative thinking in healthy volunteers. Neuropharmacology 64:490–495

    PubMed Central  PubMed  Google Scholar 

  • Murck H, Antonijevic IA, Frieboes RM et al (1999) Galanin has REM-sleep deprivation-like effects on the sleep EEG in healthy young men. J Psychiatr Res 33:225–232

    CAS  PubMed  Google Scholar 

  • Murphy PR, O’Connell RG, O’Sullivan M et al (2014) Pupil diameter covaries with BOLD activity in human locus coeruleus. Hum Brain Mapp. doi:10.1002/hbm.22466

    Google Scholar 

  • Myers CS, Taylor RC, Salmeron BJ et al (2013) Nicotine enhances alerting, but not executive, attention in smokers and nonsmokers. Nicotine Tob Res 15:277–281

    PubMed Central  PubMed  Google Scholar 

  • Nelson LE, Guo TZ, Lu J et al (2002) The sedative component of anesthesia is mediated by GABAA receptors in an endogenous sleep pathway. Nat Neurosci 5:979–984

    CAS  PubMed  Google Scholar 

  • Nelson LE, Lu J, Guo TZ et al (2003) The α2-adrenoceptor agonist dexmedetomidine converges on an endogenous sleep-promoting pathway to exert its sedative effects. Anesthesiology 98:428–436

    CAS  PubMed  Google Scholar 

  • Niepel G, Bibani RH, Vilisaar J et al (2013) Association of a deficit of arousal with fatigue in multiple sclerosis: effect of modafinil. Neuropharmacology 64:380–388

    CAS  PubMed  Google Scholar 

  • Niewenhuys R (1985) Chemoarchitecture of the brain. Springer, Berlin

    Google Scholar 

  • Nishino S, Mao J, Sampathkumaran R et al (1998) Increased dopaminergic transmission mediates the wake-promoting effects of CNS stimulants. Sleep Res Online 1:49–61

    CAS  PubMed  Google Scholar 

  • Niswender CM, Conn PJ (2010) Metabotropic glutamate receptors: physiology, pharmacology, and disease. Annu Rev Pharmacol Toxicol 50:295–322

    CAS  PubMed Central  PubMed  Google Scholar 

  • Nutt DJ, Stahl SM (2010) Searching for perfect sleep: evolution of GABAA receptor modulators as hypnotics. J Psychopharmacol 24:1601–1612

    CAS  PubMed  Google Scholar 

  • Ögren SO, Kuteeva E, Hökfelt T et al (2006) Galanin receptor antagonists: a potential novel pharmacological treatment for mood disorders. CNS Drugs 20:633–654

    PubMed  Google Scholar 

  • Ohno K, Sakurai T (2008) Orexin neuronal circuitry: role in the regulation of sleep and wakefulness. Front Neuroendocrin 29:70–87

    CAS  Google Scholar 

  • Pandi-Perumal SR, Srinivasan V, Mastroni GJM et al (2006) Melatonin: nature’s most versatile signal? FEBS J 273:2813–2838

    CAS  PubMed  Google Scholar 

  • Paqueron X, Lumbroso A, Mergoni P et al (2002) Is morphine-induced sedation synonymous with analgesia during intravenous morphine titration? Br J Anaesth 89:697–701

    CAS  PubMed  Google Scholar 

  • Parissis D, Mellidis C, Boutis A et al (2003) Neurological findings in a case of coma secondary to Datura stramonium poisoning. Eur J Neurol 10:745–746

    CAS  PubMed  Google Scholar 

  • Parmentier AC, Guhennec C et al (2007) The brain H3 receptor as a novel therapeutic target for vigilance and sleep-wake disorders. Biochem Pharmacol 73:1157–1171

    CAS  PubMed  Google Scholar 

  • Patat A, Rosenzweig P, Miget N et al (1999) Effects of 50 mg amisulpride on EEG, psychomotor and cognitive functions in healthy sleep-deprived subjects. Fundam Clin Pharmacol 13:582–594

    CAS  PubMed  Google Scholar 

  • Peever J (2011) Control of motoneuron function and masseter muscle tone during REM sleep, REM sleep behaviour disorder and cataplexy/narcolepsy. Arch Ital Biol 149:454–466

    CAS  PubMed  Google Scholar 

  • Peigneux P, Laureys S, Fuchs S et al (2001) Generation of rapid eye movements during paradoxical sleep in humans. NeuroImage 14:701–708

    CAS  PubMed  Google Scholar 

  • Pertovaara A, Haapaalinna A, Sirviö J et al (2005) Pharmacological properties, central nervous system effects, and potential therapeutic application of atipamezole, a selective alpha2-adrenoceptor antagonist. CNS Drug Rev 11:273–288

    CAS  PubMed  Google Scholar 

  • Petit-Pedrol M, Armangue T, Peng X et al (2014) Encephalitis with refractory seizures, status epilepticus, and antibodies to the GABAA receptor: a case series, characterisation of the antigen, and analysis of the effects of antibodies. Lancet Neurol 13:276–286

    CAS  PubMed  Google Scholar 

  • Phillips MA, Szabadi E, Bradshaw CM (2000) Comparison of the effects of clonidine and yohimbine on spontaneous pupillary fluctuations in healthy human volunteers. Psychopharmacology 150:85–89

    CAS  PubMed  Google Scholar 

  • Pinard A, Seddick R, Bettler B (2010) GABAB receptors: physiological functions and mechanisms of diversity. Adv Pharmacol 58:231–255

    CAS  PubMed  Google Scholar 

  • Porkka-Heiskanen T (2013) Sleep homeostasis. Curr Opin Neurobiol 23:799–805

    CAS  PubMed  Google Scholar 

  • Poulsen CF, Simeone TA, Mar TE et al (2004) Modulation by topiramate of AMPA and kainite mediated calcium influx in cultured cerebral cortical, hippocampal and cerebellar neurons. Neurochem Res 29:275–282

    CAS  PubMed  Google Scholar 

  • Proctor A, Bianchi MT (2012) Clinical pharmacology in sleep medicine. ISRN Pharmacol (Article ID 914168). doi:10.5402/2012/914168

  • Qiu M-H, Liu W, Qu W-M (2012) The role of nucleus accumbens core/shell in sleep-wake regulation and their involvement in modafinil-induced arousal. PLoS One 7:e45471

    CAS  PubMed Central  PubMed  Google Scholar 

  • Rajarao SJ, Platt B, Sukoff SJ et al (2007) Anxiolytic-like activity of the non-selective galanin receptor agonist, galnon. Neuropeptides 41:307–320

    CAS  PubMed  Google Scholar 

  • Ramamoorthy S, Bauman AL, Moore KR et al (1993) Antidepressant- and cocaine-sensitive human serotonin transporter: molecular cloning, expression, and chromosomal localization. Proc Natl Acad Sci USA 90:2542–2546

    CAS  PubMed Central  PubMed  Google Scholar 

  • Rao U, Lin KM, Schramm P et al (2004) REM sleep and cortisol responses to scopolamine during depression and remission in women. Int J Neuropsychopharmacol 7:265–274

    CAS  PubMed  Google Scholar 

  • Reynolds GP (2012) Histamine and antipsychotic drug-induced weight gain. J Psychopharmacol 26:1608–1609

    CAS  PubMed  Google Scholar 

  • Riddle EL, Fleckenstein AE, Hanson GR (2005) Role of monoamine transporters in mediating psychostimulant effects. AAPS J 7:E847–851

    CAS  PubMed Central  PubMed  Google Scholar 

  • Roth T, Lines C, Vandormael K et al (2010) Effect of gaboxadol on patient-reported measures of sleep and waking function in patients with primary insomnia: results from two randomized, controlled, 3-month studies. J Clin Sleep Med 6:30–39

    PubMed Central  PubMed  Google Scholar 

  • Rudolph U (2004) GABAergic system. In: Offermanns S, Rosehthal W (eds) Encyclopedic reference of molecular pharmacology. Springer, Berlin, pp 373–378

    Google Scholar 

  • Rudolph U, Knoflach F (2011) Beyond classical benzodiazepines: novel therapeutic potential of GABAA receptor subtypes. Nat Rev Drug Discov 10:685–697

    CAS  PubMed Central  PubMed  Google Scholar 

  • Rye D (2014) Paralysis lost: a new cause for a common parasomnia? Lancet Neurol 13:531–532

    PubMed  Google Scholar 

  • Sakai T (2013) Orexin deficiency and narcolepsy. Curr Opin Neurobiol 23:760–766

    Google Scholar 

  • Samuels ER, Szabadi E (2008a) Functional neuroanatomy of the noradrenergic locus coeruleus: its roles in the regulation of arousal and autonomic function. Part I: principles of functional organisation. Curr Neuropharmacol 6:235–253

    CAS  PubMed Central  PubMed  Google Scholar 

  • Samuels ER, Szabadi E (2008b) Functional neuroanatomy of the noradrenergic locus coeruleus: its roles in the regulation of arousal and autonomic function. Part II: physiological and pharmacological manipulations and pathological alterations of locus coeruleus activity in humans. Curr Neuropharmacol 6:254–285

    CAS  PubMed Central  PubMed  Google Scholar 

  • Samuels ER, Hou RH, Langley RW et al (2006) Comparison of pramipexole and modafinil on arousal, autonomic and endocrine functions in healthy volunteers. J Psychopharmacol 20:756–770

    CAS  PubMed  Google Scholar 

  • Sánchez-López A, Escudero M (2011) Tonic and phasic components of eye movements during REM sleep in the rat. Eur J Neurosci 33:2129–2138

    PubMed  Google Scholar 

  • Santana N, Mengod G, Artigas F (2013) Expression of α1-adrenergic receptors in rat prefrontal cortex: cellular co-localization with 5-HT2A receptors. Int J Neuropsychopharmacol 16:1139–1151

    CAS  PubMed  Google Scholar 

  • Santucci V, Glatt A, Demieville H et al (1981) Quantification of slow wave EEG induced by atropine: effects of physostigmine, amphetamine and haloperidol. Eur J Pharmacol 73:113–122

    CAS  PubMed  Google Scholar 

  • Saper CB, Fuller PM, Pedersen NP et al (2010) Sleep state switching. Neuron 68:1023–1042

    CAS  PubMed Central  PubMed  Google Scholar 

  • Scammell TE, Gershchenko DY, Mochizuki T et al (2001) An adenosine A2a agonist increases sleep and induces Fos in ventrolateral preoptic neurons. Neuroscience 107:653–663

    CAS  PubMed  Google Scholar 

  • Scheife R, Takeda M (2005) Central nervous system safety of anticholinergic drugs for the treatment of overactive bladder in the elderly. Clin Ther 27:144–153

    CAS  PubMed  Google Scholar 

  • Scheinin M, Kallio A, Koulu M (1987) Sedative and cardiovascular effects of medetomidine, a novel selective alpha 2-adrenoceptor agonist, in healthy volunteers. Br J Clin Pharmacol 24:443–451

    CAS  PubMed Central  PubMed  Google Scholar 

  • Schredl M, Hornung O, Regen F (2006) The effect of donepezil on sleep in elderly, healthy persons: a double-blind placebo-controlled study. Pharmacopsychiatry 39:205–208

    CAS  PubMed  Google Scholar 

  • Schwartz J-C (2011) The histamine H3 receptor: from discovery to clinical trials with pitolisant. Br J Pharmacol 163:713–721

    CAS  PubMed Central  PubMed  Google Scholar 

  • Schwarz RD, Callahan MJ, Coughenour LL (1999) Milameline (Cl-979/RU35926): a muscarinic receptor agonist with cognition-activating properties: biochemical and in vivo characterization. J Pharmacol Exp Ther 291:812–822

    CAS  PubMed  Google Scholar 

  • Seutin V, Franchimont N, Massotte L et al (1990) Comparison of the effect of morphine on locus coeruleus noradrenergic and ventral tegmental area dopaminergic neurons in vitro. Life Sci 46:1879–1885

    CAS  PubMed  Google Scholar 

  • Shore PA (1962) Release of serotonin and catecholamines by drugs. Pharmacol Rev 14:531–550

    CAS  PubMed  Google Scholar 

  • Sigel E, Steinmann ME (2012) Structure, function, and modulation of GABAA receptors. J Biol Chem 287:40224–40231

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sitaram N, Moore AM, Gillin JC (1978) The effect of physostigmine on normal human sleep and dreaming. Arch Gen Psychiatry 35:1239–1243

    CAS  PubMed  Google Scholar 

  • Stäubli U, Scafidi J, Chun D (1999) GABAB receptor antagonism: facilitatory effects on memory parallel those on LTP induced by TBS but not HFS. J Neurosci 19:4609–4615

    PubMed  Google Scholar 

  • Steiger A (2007) Neurochemical regulation of sleep. J Psychiatr Res 41:537–552

    PubMed  Google Scholar 

  • Sterpenich V, D’Argembeau A, Desseilles M et al (2006) The locus ceruleus is involved in the successful retrieval of emotional memories in humans. J Neurosci 26:7416–7423

    CAS  PubMed  Google Scholar 

  • Sulser F, Bass AD (1968) Pharmacodynamic and biochemical considerations on the mode of action of reserpine-like drugs. In: Efron DH, Cole JO, Levine J et al (eds) Psychopharmacology: a review of progress 1957–1967. Public Health Service Publication No 1836. Washington, DC, pp 1093–1100

    Google Scholar 

  • Szabadi E (2012) Modulation of physiological reflexes by pain: role of the locus coeruleus. Front Integr Neurosci 6:1–15 (Article 94)

    Google Scholar 

  • Szabadi E (2013) Functional neuroanatomy of the central noradrenergic system. J Psychopharmacol 27:659–693

    CAS  PubMed  Google Scholar 

  • Szabadi E (2014) Selective targets for arousal-modifying drugs: implications for the treatment of sleep disorders. Drug Discov Today 19:701–708

    CAS  PubMed  Google Scholar 

  • Szabadi E, Bradshaw CM (2000) Mechanisms of action of reboxetine. Rev Contemp Pharmacother 11:267–282

    CAS  Google Scholar 

  • Taberan IV (2013) Functional pharmacology of histamine H1 receptors expressed in mouse preoptic/anterior hypothalamic neurons. Br J Pharmacol 170:415–425

    Google Scholar 

  • Tafti M (2007) Reply to ‘Promotion of sleep by targeting the orexin system in rats, dogs and humans’. Nat Med 13:525–526

    CAS  PubMed  Google Scholar 

  • Thakkar MM (2011) Histamine in the regulation of wakefulness. Sleep Med Rev 15:65–74

    PubMed Central  PubMed  Google Scholar 

  • Torterolo P, Morales FR, Chase MH (2002) GABAergic mechanisms in the pedunculopontine tegmental nucleus of the cat promote active (REM) sleep. Brain Res 944:1–9

    CAS  PubMed  Google Scholar 

  • Triarhou LC (2006) The percipient observations of Constantin von Economo on encephalitis lethargica and sleep disruption and their lasting impact on contemporary sleep research. Brain Res Bull 69:244–258

    PubMed  Google Scholar 

  • Tsunematsu T, Ueno T, Tabuchi S et al (2014) Optogenetic manipulation of activity and temporally controlled cell-specific ablation reveal a role for MCH neurons in sleep/wake regulation. J Neurosci 34:6896–6909

    CAS  PubMed Central  PubMed  Google Scholar 

  • Van den Heuvel CJ, Reid KJ, Dawson D (1997) Effect of atenolol on nocturnal sleep and temperature in young men: reversal by pharmacological doses of melatonin. Physiol Behav 61:795–802

    Google Scholar 

  • Vandewalle G, Schmidt C, Albouy G et al (2007) Brain responses to violet, blue and green monochromatic light exposures in humans: prominent role of blue light and the brainstem. PLoS One 2(11):e1247

    PubMed Central  PubMed  Google Scholar 

  • Vanover KE, Davis RE (2010) Role of 5-HT2A receptor antagonists in the treatment of insomnia. Nat Sci Sleep 2:139–150

    PubMed Central  PubMed  Google Scholar 

  • Venault P, Chapouthier G (2007) From behavioural pharmacology of beta-carbolines to seizures, anxiety, and memory. ScientificWorldJournal 7:204–223

    CAS  PubMed  Google Scholar 

  • Verster JC, Veldhuijzen DS, Volkerts ER (2006) Effects of an opioid (oxycodone/paracetamol) and an NSAID (bromfenac) on driving ability, memory functioning, psychomotor performance, pupil size, and mood. Clin J Pain 22:499–504

    PubMed  Google Scholar 

  • Votava Z, Benesová O, Bohdanecký Z et al (1968) Influence of atropine, scopolamine and benactyzine on the physostigmine arousal reaction in rabbits. Prog Brain Res 28:40–47

    CAS  PubMed  Google Scholar 

  • Webling KE, Runesson J, Bartfai T et al (2012) Galanin receptors and ligands. Front Endocrinol (Lausanne) 3:146

    Google Scholar 

  • Weinhold SL, Seeck-Hirschner NA et al (2014) The effect of intranasal orexin-A (hypocretin-1) on sleep, wakefulness and attention in narcolepsy with cataplexy. Behav Brain Res 262:8–13

    CAS  PubMed  Google Scholar 

  • Wilhelm B, Giedke H, Lϋdtke H et al (2001) Daytime variations in central nervous system activation measured by a pupillographic sleepiness test. J Sleep Res 10:1–7

    CAS  PubMed  Google Scholar 

  • Wilson SJ, Nutt DJ, Alford C et al (2010) British Association for Psychopharmacology consensus statement on evidence-based treatment of insomnia, parasomnias and circadian rhythm disorders. J Pschopharmacol 24:1577–1600

    CAS  Google Scholar 

  • Winokur A, Gary KA, Rodner S et al (2001) Depression, sleep physiology, and antidepressant drugs. Depress Anxiety 14:19–28

    CAS  PubMed  Google Scholar 

  • Winsky-Sommerer R (2009) Role of GABAA receptors in the physiology and pharmacology of sleep. Eur J Neurosci 29:1779–1794

    PubMed  Google Scholar 

  • Wisor J (2013) Modafinil as a catecholaminergic agent: empirical evidence and unanswered questions. Front Neurol 4:139 (eCollection 2013)

    PubMed Central  PubMed  Google Scholar 

  • Wu MF, Gulyani SA, Yau E et al (1999) Locus coeruleus neurons: cessation of activity during cataplexy. Neuroscience 91:1389–1399

    CAS  PubMed  Google Scholar 

  • Zant JC, Rozov S, Wigren HK et al (2012) Histamine release in the basal forebrain mediates cortical activation through cholinergic neurons. J Neurosci 32:13244–13254

    CAS  PubMed  Google Scholar 

  • Zecharia AY, Yu X, Götz T et al (2012) GABAergic inhibition of histaminergic neurons regulates active waking but not the sleep-wake switch or propofol-induced loss of consciousness. J Neurosci 32:13062–13075

    CAS  PubMed Central  PubMed  Google Scholar 

  • Zhang J-P, Qi X, Yuan X-S et al (2013) Projections of nucleus accumbens adenosine A2A receptor neurons in the mouse brain and their implications in medicating sleep-wake regulations. Front Neuroanat 7:1–15 (Article 43)

    Google Scholar 

  • Zheng G, Dwoskin LP, Crooks PA (2006) Vesicular monoamine transporter 2: role as a novel target for drug development. AAPS J 8:E682–E692

    PubMed Central  PubMed  Google Scholar 

  • Zhu J, Reith MEA (2008) Role of dopamine transporter in the action of psychostimulants, nicotine, and other drugs of abuse. CNS Neurol Disord Drug Targets 7:393–409

    CAS  PubMed Central  PubMed  Google Scholar 

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Acknowledgement

I am grateful to Rob Langley for drawing the figures.

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    Elemer Szabadi

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Szabadi, E. (2015). Neuronal Networks Regulating Sleep and Arousal: Effect of Drugs. In: Guglietta, A. (eds) Drug Treatment of Sleep Disorders. Milestones in Drug Therapy. Springer, Cham. https://doi.org/10.1007/978-3-319-11514-6_2

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