Neurochemical Research

, Volume 43, Issue 6, pp 1171–1181 | Cite as

Evaluation of Neurotransmitter Alterations in Four Distinct Brain Regions After Rapid Eye Movement Sleep Deprivation (REMSD) Induced Mania-Like Behaviour in Swiss Albino Mice

  • Saiful Alom Siddique
  • Thangavel Tamilselvan
  • Manikkannan Vishnupriya
  • Elumalai BalamuruganEmail author
Original Paper


A number of neurotransmitter systems have been implicated in contributing to the pathology of mood disorders, including those of dopamine (DA), serotonin (5-HT), norepinephrine (NE) and γ-aminobutyric acid (GABA). Rapid eye movement sleep deprivation (REMSD) alters most of the neurotransmitters, which may have adverse behavioural changes and other health consequences like mania and other psychiatric disorders. The exact role of REMSD altered neurotransmitter levels and the manner in which emerging consequences lead to mania-like behaviour is poorly understood. Thus, we sought to verify the levels of neurotransmitter changes after 48, 72 and 96 h of REMSD induced mania-like behaviour in mice. We performed modified multiple platform (MMP) method of depriving the REM sleep and one group maintained as a control. To measure the hyperactivity through locomotion, exploration and behavioural despair, we performed the Open Field Test (OFT) and the Forced Swim Test (FST). Quantitative determinations of DA, 5-HT, NE and GABA concentrations in four distinct brain regions (cerebral cortex, hippocampus, midbrain, and pons) were determined by the spectrofluorimetric method. These experiments showed higher locomotion and increased swimming, struggling/climbing and decreased mobility among REMSD animals as well as disrupted concentrations of the majority of the studied neurotransmitters during REMSD. Our study indicated that REMSD results in mania-like behaviour in mice and associated disruption to neurotransmitter levels, although the exact mechanisms by which these take place remain to be determined.


Rapid eye movement sleep deprivation Mania Bipolar disorder Neurotransmitter Modified multiple platform method 



Department of Science and Technology (DST), INSPIRE division, New Delhi provided financial support as a fellowship (Grant Reference Number—DST/INSPIRE/2014/IF140562) to carry out this research. The funding source had no involvement in the preparation of the article, study design, collection, analysis and interpretation of data, writing of the report or decision to submit the article for publication.

Compliance with Ethical Standards

Conflict of interest

The authors declare that there are no conflicts of interest.


  1. 1.
    American Psychiatric Association (1994) Diagnostic and statistical manual of mental disorders. DSM-IV, 4th edn. American Psychiatric Association, Washington, DCGoogle Scholar
  2. 2.
    Merikangas KR, Jin R, He JP, Kessler RC, Lee S, Sampson NA, Viana MC, Andrade LH, Hu C, Karam EG, Ladea M, Medina-Mora ME, Ono Y, Posada-Villa J, Sagar R, Wells JE, Zarkov Z (2011) Prevalence and correlates of bipolar spectrum disorder in the world mental health survey initiative. Arch Gen Psychiatry 68(3):241–251CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Jansen K, Ores Lda C, Cardoso Tde A, Lima Rda C, Souza LD, Magalhães PV, Pinheiro RT, da Silva RA (2011) Prevalence of episodes of mania and hypomania and associated comorbidities among young adults. J Affect Disord 130:328–333CrossRefPubMedGoogle Scholar
  4. 4.
    Dilsaver SC (2011) An estimate of the minimum economic burden of bipolar I and II disorders in the United States 2009. J Affect Disord 129(1–3):79–83CrossRefPubMedGoogle Scholar
  5. 5.
    McNamara P, Capellini I, Harris E, Nunn CL, Barton RA, Preston B (2008) The phylogeny of sleep database: a new resource for sleep scientists. Open Sleep J 1:11–14CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Cantero JL, Atienza M, Stickgold R, Kahana MJ, Madsen JR, Kocsis B (2003) Sleep-dependent theta oscillations in the human hippocampus and neocortex. J Neurosci 23(34):10897–10903CrossRefPubMedGoogle Scholar
  7. 7.
    Buzsáki G (2002) Theta oscillations in the hippocampus. Neuron 33:325–340CrossRefPubMedGoogle Scholar
  8. 8.
    Hublin C, Kaprio J, Partinen M, Koskenvuo M (2001) Insufficient sleep—a population-based study in adults. Sleep 24:392–400CrossRefPubMedGoogle Scholar
  9. 9.
    Rajaratnam SM, Arendt J (2001) Health in a 24-h society. Lancet 358(9286):999–1005CrossRefPubMedGoogle Scholar
  10. 10.
    National Health Interview Survey (2005) Quickstats percentage of adults who reported an average of < 6 hours of sleep per 24-hour period bSaAG-US. MMWR Morb Mortal Wkly Rep 54:933Google Scholar
  11. 11.
    Centers for Disease Control and Prevention (2011) Effect of short sleep duration on daily activities—United States 2005–2008. MMWR Morb Mortal Wkly Rep 60(8):239–242Google Scholar
  12. 12.
    Vogel GW (1999) REM sleep deprivation and behavioral changes In Mallick BN, Inoue S (eds) Rapid eye movement sleep. Marcel Dekker, New York, pp 355–366Google Scholar
  13. 13.
    Harvey AG (2008) Sleep and circadian rhythms in bipolar disorder seeking synchrony harmony and regulation. Am J Psychiatry 165:820–829CrossRefPubMedGoogle Scholar
  14. 14.
    Serra G, Argiolas A, Klimek V, Fadda F, Gessa GL (1979) Chronic treatment with antidepressants prevents the inhibitory effect of small doses of apomorphine on dopamine synthesis and motor activity. Life Sci 25:415–423CrossRefPubMedGoogle Scholar
  15. 15.
    van Praag HM, Korf J (1975) Central monoamine deficiency in depressions: causative of secondary phenomenon? Pharmakopsychiatr Neuropsychopharmakol 8(5):322–326CrossRefPubMedGoogle Scholar
  16. 16.
    Bannerman DM, Rawlins JN, McHugh SB, Deacon RM, Yee BK, Bast T, Zhang WN, Pothuizen HH, Feldon J (2004) Regional dissociations within the hippocampus—memory and anxiety. Neurosci Biobehav Rev 28(3):273–283CrossRefPubMedGoogle Scholar
  17. 17.
    Moore RY, Halaris AE (1975) Hippocampal innervation by serotonin neurons of the midbrain raphe in the rat. J Comp Neurol 164(2):171–183CrossRefPubMedGoogle Scholar
  18. 18.
    Vadodaria KC, Stern S, Marchetto MC, Gage FH (2017) Serotonin in psychiatry: in vitro disease modeling using patient-derived neurons. Cell Tissue Res 371(1):161–170CrossRefPubMedGoogle Scholar
  19. 19.
    Derry C, Benjamin C, Bladin P, le Bars D, Tochon-Danguy H, Berkovic SF, Zimmer L, Costes N, Mulligan R, Reutens D (2006) Increased serotonin receptor availability in human sleep: evidence from an [18F]MPPF PET study in narcolepsy. Neuroimage 30(2):341–348CrossRefPubMedGoogle Scholar
  20. 20.
    Graeff FG, Guimarães FS, De Andrade TG, Deakin JF (1996) Role of 5-HT in stress, anxiety, and depression. Pharmacol Biochem Behav 54(1):129–141CrossRefPubMedGoogle Scholar
  21. 21.
    Schildkraut JJ (1965) The catecholamine hypothesis of affective disorders: a review of supportive evidence. Am J Psychiatry 122(5):509–522CrossRefPubMedGoogle Scholar
  22. 22.
    Zachmann M, Tocci P, Nyhan WL (1966) The occurrence of gamma aminobutyric acid in human tissues other than brain. J Biol Chem 241(6):1355–1358PubMedGoogle Scholar
  23. 23.
    Otsuka M, Iversen LL, Hall ZW, Kravitz EA (1966) Release of gamma aminobutyric acid from inhibitory nerves of lobster. Proc Natl Acad Sci USA 56:1110–1115CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Emrich HM, von Zerssen D, Kissling W, Moller HJ, Windorfer A (1980) Effect of sodium valproate on mania. The GABA-hypothesis of affective disorders. Arch Psychiatr Nervenkrankh 229:1–16CrossRefGoogle Scholar
  25. 25.
    Massat I, Sourey D, Papadimitriou GN, Mendlewicz J (2000) The GABAergic hypothesis of mood disorders. In: Soares JC, GershonS (eds) Bipolar disorders, basic mechanisms and therapeutic implication. Marcel Dekker, New York, pp 143–165Google Scholar
  26. 26.
    Brady RO Jr, McCarthy JM, Prescot AP, Jensen JE, Cooper AJ, Cohen BM, Renshaw PF, Ongür D (2013) Brain gamma-aminobutyric acid (GABA) abnormalities in bipolar disorder. Bipolar Disord 15(4):434–439CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Jouvet D, Vimont P, Delorme F, Jouvet M (1964) Study of selective deprivation of the paradoxal sleep phase in the cat. C R Seances Soc Biol Fil 158:756–759PubMedGoogle Scholar
  28. 28.
    Nunes JRGP., Tufik S (1994) Validation of the modified multiple platform method (MMP) of paradoxical sleep deprivation in rats. Sleep Res 23:419Google Scholar
  29. 29.
    Walsh RN, Cummins RA (1976) The open field test a critical review. Psychol Bull 83:482–404CrossRefPubMedGoogle Scholar
  30. 30.
    Detke MJ, Lucki I (1996) Detection of serotonergic and noradrenergic antidepressants in the rat forced swimming test the effects of water depth. Behav Brain Res 73(1–2):43–46PubMedGoogle Scholar
  31. 31.
    Schlumpf M, Lichtensteiger W, Langemann H, Waser PG, Hefti F (1974) A fluorometric micro method for the simultaneous determination of serotonin, noradrenaline and dopamine in milligram amounts of brain tissue. Biochem Pharmacol 23(17):2437–2446CrossRefPubMedGoogle Scholar
  32. 32.
    Lowe IP, Robins E, Eyerman GS (1958) The fluorometric measurement of glutamic decarboxylase and its distribution in brain. J Neurochem 3:8–18CrossRefPubMedGoogle Scholar
  33. 33.
    Weber F, Hoang Do JP, Chung S, Beier KT, Bikov M, Saffari Doost M, Dan Y (2018) Regulation of REM and non-REM sleep by periaqueductal GABAergic neurons. Nat Commun 9(1):354CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Siegel JM, Nienhuis R, Tomaszewski KS (1984) REM sleep signs rostral to chronic transections at the pontomedullary junction. Neurosci Lett 45:241–246CrossRefPubMedGoogle Scholar
  35. 35.
    Barbosa FJ, Hesse B, de Almeida RB, Baretta IP, Boerngen-Lacerda R, Andreatini R (2011) Magnesium sulfate and sodium valproate block methylphenidate induced hyperlocomotion an animal model of mania. Pharmacol Rep 63:64–70CrossRefPubMedGoogle Scholar
  36. 36.
    Berns GS, Nemeroff CB (2003) The neurobiology of bipolar disorder. Am J Med Genet C 123C(1):76–84CrossRefGoogle Scholar
  37. 37.
    Machado-Vieira R, Kapczinski F, Soares JC (2004) Perspectives for the development of animal models of bipolar disorder. Prog Neuropsychopharmacol Biol Psychiatry 28(2):209–224CrossRefPubMedGoogle Scholar
  38. 38.
    Decker S, Grider G, Cobb M, Li XP, Huff MO, El-Mallakh RS, Levy RS (2000) Open field is more sensitive than automated activity monitor in documenting ouabain-induced hyperlocomotion in the development of an animal model for bipolar illness. Prog Neuropsychopharmacol Biol Psychiatry 24:455–462CrossRefPubMedGoogle Scholar
  39. 39.
    Armani F, Andersen ML, Andreatini R, Frussa-Filho R, Tufik S, Galduróz JC (2012) Successful combined therapy with tamoxifen and lithium in a paradoxical sleep deprivation-induced mania model. CNS Neurosci Ther 18(2):119–125CrossRefPubMedGoogle Scholar
  40. 40.
    Tamilselvan T, Siddique SA, Vishnupriya M, Sindhu G, Balamurugan E (2017) Behavioral and neurochemical evaluation of ethanol on olanzapine treated methylphenidate induced manic like behaviors in swiss albino mice. Beni-Suef Univ J Basic Appl Sci 6(1):48–56CrossRefGoogle Scholar
  41. 41.
    Trulson ME (1985) Activity of dopamine-containing substantia nigra neurons in freely moving cats. Neurosci Biobehav Rev 9:283–297CrossRefPubMedGoogle Scholar
  42. 42.
    Wisor JP, Nishino S, Sora I, Uhl GH, Mignot E, Edgar DM (2001) Dopaminergic role in stimulant-induced wakefulness. J Neurosci 21(5):1787–1794CrossRefPubMedGoogle Scholar
  43. 43.
    Monti JM, Fernandez M, Jantos H (1990) Sleep during acute dopamine D1 agonist SKF 38393 or D1 antagonist SCH 23390 administration in rats. Neuropsychopharmacology 3(3):153–162PubMedGoogle Scholar
  44. 44.
    Nestler EJ, Carlezon WA Jr (2006) The mesolimbic dopamine reward circuit depression. Biol Psychiatry 59:1151–1159CrossRefPubMedGoogle Scholar
  45. 45.
    Chung S, Lee EJ, Yun S, Choe HK, Park SB, Son HJ, Kim KS, Dluzen DE, Lee I, Hwang O, Son GH, Kim K (2014) Impact of circadian nuclear receptor REV-ERBα on midbrain dopamine production and mood regulation. Cell 157:858–868CrossRefPubMedGoogle Scholar
  46. 46.
    Cousins DA, Butts K, Young AH (2009) The role of dopamine in bipolar disorder. Bipolar Disord 11:787–806CrossRefPubMedGoogle Scholar
  47. 47.
    Wightman RM, Robinson DL (2002) Transient changes in mesolimbic dopamine and their association with ‘reward’. J Neurochem 82:721–735CrossRefPubMedGoogle Scholar
  48. 48.
    Berk M, Dodd S, Kauer-Sant’anna M, Malhi GS, Bourin M, Kapczinski F, Norman T (2007) Dopamine dysregulation syndrome: implications for a dopamine hypothesis of bipolar disorder. Acta Psychiatr Scand 116(Suppl 434):41–49CrossRefGoogle Scholar
  49. 49.
    Anand A, Barkay G, Dzemidzic M, Albrecht D, Karne H, Zheng QH, Hutchins GD, Normandin MD, Yoder KK (2011) Striatal dopamine transporter availability in unmedicated bipolar disorder. Bipolar Disord 13:406–413CrossRefPubMedGoogle Scholar
  50. 50.
    Young JW, van Enkhuizen J, Winstanley CA, Greyer MA (2011) Increased risk-taking behavior in dopamine transporter knockdown mice further support for a mouse model of mania. J Psychopharmacol 25:934–943CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Vadodaria KC, Stern S, Marchetto MC, Gage FH (2018) Serotonin in psychiatry: in vitro disease modeling using patient-derived neurons. Cell Tissue Res 371(1):161–170CrossRefPubMedGoogle Scholar
  52. 52.
    Gardner JP, Fornal CA, Jacobs BL (1997) Effects of sleep deprivation on serotonergic neuronal activity in the dorsal raphe nucleus of the freely moving cat. Neuropsychopharmacology 17:72–81CrossRefPubMedGoogle Scholar
  53. 53.
    Lopez-Rodriguez F, Wilson CL, Maidment NT, Poland RE, Engel J (2003) Total sleep deprivation increases extracellular serotonin in the rat hippocampus. Neuroscience 121:523–530CrossRefPubMedGoogle Scholar
  54. 54.
    Peñalva RG, Lancel M, Flachskamm C, Reul JM, Holsboer F, Linthorst AC (2003) Effect of sleep and sleep deprivation on serotonergic neurotransmission in the hippocampus: a combined in vivo microdialysis/EEG study in rats. Eur J Neurosci 17(9):1896–1906CrossRefPubMedGoogle Scholar
  55. 55.
    Hoyer D, Hannon JP, Martin GR (2002) Molecular pharmacological and functional diversity of 5-HT receptors. Pharmacol Biochem Behav 71:533–554CrossRefPubMedGoogle Scholar
  56. 56.
    Moore RY, Halaris AE (1975) Hippocampal innervation by serotonin neurons of the midbrain raphe in the rat. J Comp Neurol 164:171–183CrossRefPubMedGoogle Scholar
  57. 57.
    Dale E, Pehrson AL, Jeyarajah T, Li Y, Leiser SC, Smagin G, Olsen CK, Sanchez C (2016) Effects of serotonin in the hippocampus how SSRIs and multimodal antidepressants might regulate pyramidal cell function. CNS Spectr 21:143–161CrossRefPubMedGoogle Scholar
  58. 58.
    Gonzalez-Maeso J, Ang RL, Yuen T, Chan P, Weisstaub NV, Lopez-Gimenez JF, Zhou M, Okawa Y, Callado LF, Milligan G, Gingrich JA, Filizola M, Meana JJ, Sealfon SC (2008) Identification of a serotonin/glutamate receptor complex implicated in psychosis. Nature 452:93–97CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Moreno JL, Holloway T, Albizu L, Sealfon SC, Gonzalez-Maeso J (2011) Metabotropic glutamate mGlu2 receptor is necessary for the pharmacological and behavioral effects induced by hallucinogenic 5-HT2A receptor agonists. Neurosci Lett 493:76–79CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Portas CM, Bjorvatn B, Ursin R (2000) Serotonin and the sleep/wake cycle special emphasis on microdialysis studies. Prog Neurobiol 60:13–35CrossRefPubMedGoogle Scholar
  61. 61.
    Monti JM, Jantos H (2008) The roles of dopamine and serotonin and of their receptors in regulating sleep and waking. Prog Brain Res 172:625–646CrossRefPubMedGoogle Scholar
  62. 62.
    Wu JC, Bunney WE (1990) The biological basis of an antidepressant response to sleep deprivation and relapse: review and hypothesis. Am J Psychiatry 147:14–21CrossRefPubMedGoogle Scholar
  63. 63.
    Adrien J (2002) Neurobiological bases for the relation between sleep and depression. Sleep Med Rev 6:341–351CrossRefPubMedGoogle Scholar
  64. 64.
    Berridge CW, Waterhouse BD (2003) The locus coeruleus-noradrenergic system modulation of behavioral state and state-dependent cognitive processes. Brain Res Rev 42:33–84CrossRefPubMedGoogle Scholar
  65. 65.
    Foote SL, Aston-Jones G, Bloom FE (1980) Impulse activity of locus coeruleus neurons in awake rats and monkeys is a function of sensory stimulation and arousal. Proc Natl Acad Sci USA 77:3033–3037CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Aston-Jones G, Bloom FE (1981) Activity of norepinephrine-containing locus coeruleus neurons in behaving rats anticipates fluctuations in the sleep-waking cycle. J Neurosci 1(8):876–886CrossRefPubMedGoogle Scholar
  67. 67.
    Berridge CW, Abercrombie ED (1999) Relationship between locus coeruleus discharge rates and rates of norepinephrine release within neocortex as assessed by in vivo microdialysis. Neuroscience 93:1263–1270CrossRefPubMedGoogle Scholar
  68. 68.
    De Sarro GB, Ascioti C, Froio F, Libri V, Nistico G (1987) Evidence that locus coeruleus is the site where clonidine and drugs acting at alpha 1- and alpha 2-adrenoceptors affect sleep and arousal mechanisms. Br J Pharmacol 90:675–685CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Goodwin FK, Jamison KR (1990) Manic depressive illness. Oxford University Press, New YorkGoogle Scholar
  70. 70.
    Vawter MP, Freed WJ, Kleinman JE (2000) Neuropathology of bipolar disorder. Biol Psychiatry 48:486–504CrossRefPubMedGoogle Scholar
  71. 71.
    Schatzberg AF, Schildkrout JJ (1995) Recent studies on norepinephrine systems in mood disorders. In: Bloom FE, Kupfer D (eds) Psychopharmacology: the fourth generation of progress. Raven Press, NewYork, pp 911–920Google Scholar
  72. 72.
    Shastry BS (2005) Bipolar disorder: an update. Neurochem Int 46(4):273–279CrossRefPubMedGoogle Scholar
  73. 73.
    Krenzer M, Anaclet C, Vetrivelan R, Wang N, Vong L, Lowell BB, Fuller PM, Lu J (2011) Brainstem and spinal cord circuitry regulating REM sleep and muscle atonia. PLoS ONE 6(10):e24998CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    España RA, Scammell TE (2011) Sleep neurobiology from a clinical perspective. Sleep 34(7):845–858PubMedPubMedCentralGoogle Scholar
  75. 75.
    Wang PW, Sailasuta N, Chandler RA, Ketter TA (2006) Magnetic resonance spectroscopic measurement of cerebral gamma-aminobutyric acid concentrations in patients with bipolar disorders. Acta Neuropsychiatr 18:120–126CrossRefPubMedGoogle Scholar
  76. 76.
    Ongur D, Prescot AP, McCarthy J, Cohen BM, Renshaw PF (2010) Elevated gamma-aminobutyric acid levels in chronic schizophrenia. Biol Psychiatry 68:667–670CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Benes FM, Berretta S (2001) GABAergic interneurons implications for understanding schizophrenia and bipolar disorder. Neuropsychopharmacology 25:1–27CrossRefPubMedGoogle Scholar
  78. 78.
    Massat I, Souery D, Del-Favero J, Oruc L, Noethen MM, Blackwood D, Thomson M, Muir W, Papadimitriou GN, Dikeos DG, Kaneva R, Serretti A, Lilli R, Smeraldi E, Jakovljevic M, Folnegovic V, Rietschel M, Milanova V, Valente F, Van Broeckhoven C, Mendlewicz J (2002) Excess of allele1 for alpha3 subunit GABA receptor gene (GABRA3) in bipolar patients a multicentric association study. Mol Psychiatry 7:201–207CrossRefPubMedGoogle Scholar
  79. 79.
    Torrey EF, Barci BM, Webster MJ, Bartko JJ, Meador-Woodruff JH, Knable MB (2005) Neurochemical markers for schizophrenia bipolar disorder and major depression in postmortem brains. Biol Psychiatry 57:252–260CrossRefPubMedGoogle Scholar
  80. 80.
    Petty F, Kramer GL, Dunnam D, Rush AJ (1990) Plasma GABA in mood disorders. Psychopharmacol Bull 26(2):157–161PubMedGoogle Scholar
  81. 81.
    Petty F (1994) Plasma concentrations of gamma aminobutyric acid (GABA) and mood disorders a blood test for manic depressive disease? Clin Chem 40(2):296–302PubMedGoogle Scholar
  82. 82.
    Gerner RH, Fairbanks L, Anderson GM, Young JG, Scheinin M, Linnoila M, Hare TA, Shaywitz BA, Cohen DJ (1984) CSF neurochemistry in depressed manic and schizophrenic patients compared with that of normal controls. Am J Psychiatry 141:1533–1540CrossRefPubMedGoogle Scholar
  83. 83.
    Petty F, Schlesser MA (1981) Plasma GABA in affective illness: a preliminary investigation. J Affect Disord 3:339–343CrossRefPubMedGoogle Scholar
  84. 84.
    Petty F, Sherman AD (1984) Plasma GABA levels in psychiatric illness. J Affect Disord 6:131–138CrossRefPubMedGoogle Scholar
  85. 85.
    Bhagwagar Z, Wylezinska M, Jezzard P, Evans J, Ashworth F, Sule A, Matthews PM, Cowen PJ (2007) Reduction in occipital cortex gamma-aminobutyric acid concentrations in medication-free recovered unipolar depressed and bipolar subjects. Biol Psychiatry 61(6):806–812CrossRefPubMedGoogle Scholar
  86. 86.
    Benes FM, Kwok EW, Vincent SL, Todtenkopf MS (1998) A reduction of nonpyramidal cells in sector CA2 of schizophrenics and manic depressives. Biol Psychiatry 44(2):88–97CrossRefPubMedGoogle Scholar
  87. 87.
    Heckers S, Stone D, Walsh J, Shick J, Koul P, Benes FM (2002) Differential hippocampal expression of glutamic acid decarboxylase 65 and 67 messenger RNA in bipolar disorder and schizophrenia. Arch Gen Psychiatry 59(6):521–529CrossRefPubMedGoogle Scholar
  88. 88.
    Vanini G, Lydic R, Baghdoyan HA (2012) GABA-to-ACh ratio in basal forebrain and cerebral cortex varies significantly during sleep. Sleep 35(10):1325–1334CrossRefPubMedPubMedCentralGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Saiful Alom Siddique
    • 1
  • Thangavel Tamilselvan
    • 1
  • Manikkannan Vishnupriya
    • 1
  • Elumalai Balamurugan
    • 1
    Email author
  1. 1.Department of Biochemistry and Biotechnology, Faculty of ScienceAnnamalai UniversityAnnamalainagarIndia

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