Psychopharmacology

, Volume 176, Issue 2, pp 115–122 | Cite as

Anxiogenic effect of sleep deprivation in the elevated plus-maze test in mice

  • Regina H. Silva
  • Sonia R. Kameda
  • Rita C. Carvalho
  • André L. Takatsu-Coleman
  • Suzy T. Niigaki
  • Vanessa C. Abílio
  • Sergio Tufik
  • Roberto Frussa-Filho
Original Investigation

Abstract

Rationale

Several clinical studies demonstrate that the absence of periods of sleep is closely related to occurrence of anxiety symptoms. However, the basis of these interactions is poorly understood. Studies performed with animal models of sleep deprivation and anxiety would be helpful in the understanding of the mechanisms underlying this relationship, but some animal studies have not corroborated clinical data, reporting anxiolytic effects of sleep deprivation.

Objectives

The aim of the present study was to verify the effects of different protocols of sleep deprivation in mice tested in the elevated plus-maze and to assess the effect of chlordiazepoxide and clonidine.

Methods

Three-month-old male mice were sleep-deprived for 24 or 72 h using the methods of single or multiple platforms in water tanks. Mice kept in their home cages were used as controls. Plus-maze behavior was observed immediately after the deprivation period.

Results

Mice that were sleep-deprived for 72 h spent a lower percent time in the open arms of the apparatus than control animals. This sleep deprivation-induced anxiety-like behavior was unaffected by treatment with chlordiazepoxide (5.0 and 7.5 mg/kg IP), but reversed by an administration of 5 or 10 μg/kg IP clonidine.

Conclusion

The results indicate that under specific methodological conditions sleep deprivation causes an increase in anxiety-like behavior in mice exposed to the elevated plus-maze.

Keywords

Sleep deprivation Anxiety Animal model Chlordiazepoxide Clonidine 

References

  1. Albert I, Cicala GA, Siegel J (1970) The behavioral effects of REM sleep deprivation in rats. Psychophysiology 6:550–560PubMedGoogle Scholar
  2. American Psychiatry Association (1994) Diagnostic statistical manual of mental disorders, 4th edn. APA, Washington D.C.Google Scholar
  3. Bourdet C, Goldenberg F (1994) Insomnia in anxiety: sleep EEG changes. J Psychosom Res 38:93–104CrossRefPubMedGoogle Scholar
  4. Coenen AML, Van Hulzen ZJM (1980) Paradoxical sleep deprivation in animal studies: some methodological considerations. In: McConnell, Boer GJ, Romjin HJ, Van de Poss NE, Corner MA (eds) Adaptive capabilities of the nervous system (Progress in Brain Research, vol 53). Elsevier, Amsterdam, pp 325–330Google Scholar
  5. Dahl RE, Lewin DS (2002) Pathways to adolescent health sleep regulation and behavior. J Adolesc Health 31:175–184CrossRefPubMedGoogle Scholar
  6. Dinges DF, Pack F, Williams D, Gillen KA, Powell JW, Ott GE, Pack AI (1997) Cumulative sleepiness, mood disturbances, and psychomotor vigillance performance decrements during a week of sleep restricted to 4–5 hours per night. Sleep 20:267–277PubMedGoogle Scholar
  7. File SE, Zangrossi H Jr, Viana M, Graeff F (1993) Trial 2 in the elevated plus-maze: a different form of fear. Psychopharmacology 111:491–494PubMedGoogle Scholar
  8. Frussa-Filho R, Ribeiro R De A (2002) One-trial tolerance to the effects of chlordiazepoxide in the elevated plus-maze is not due to acquisition of a phobic avoidance of open arms during initial exposure. Life Sci 71:519–525CrossRefPubMedGoogle Scholar
  9. Frussa-Filho R, Barbosa-Júnior H, Silva RH, Cunha C, Mello CF (1999) Naltrexone potentiates the anxiolytic effect of chlordiazepoxide in rats exposed to novel environments. Psychopharmacology 147:168–173Google Scholar
  10. Gentsch C, Lichtsteiner M, Feer H (1987) Open field and elevated plus-maze: a behavioral comparison between spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats and the effects of chlordiazepoxide. Behav Brain Res 25:101–107CrossRefPubMedGoogle Scholar
  11. Gerner RH, Post RM, Gillin C, Bunney WE Jr (1979) Biological and behavioral effects of one night’s sleep deprivation in depressed patients and normals. J Psychiatr Res 15:21–40CrossRefPubMedGoogle Scholar
  12. Goto SH, Conceição IM, Ribeiro RA, Frussa-Filho R (1993) Comparison of anxiety measured in the elevated plus-maze, open-field and social interaction tests between spontaneously hypertensive rats and Wistar EPM-1 rats. Braz J Med Biol Res 26:965–969PubMedGoogle Scholar
  13. Gottileb DJ, Peterson CA, Parenti CM, Lofgren RP (1993) Effects of a night float system on house staff neuropsychologic function. J Gen Int Med 8:146–148PubMedGoogle Scholar
  14. Handley SL, Mithani S (1984) Effects of alpha2-adrenoceptor agonists and antagonists in a maze-exploration model of fear-motivated behavior. Naunyn Schmiedeberg′s Arch Pharmacol 327:1–5PubMedGoogle Scholar
  15. Hicks RA, Adams G (1976) REM sleep deprivation and exploration in young rats. Psychol Rep 38:1154PubMedGoogle Scholar
  16. Hipólide DC, Tufik S, Raymond R, Nobrega JN (1998) Heterogenous effects of rapid eye movement sleep deprivation on binding to alpha- and beta-adrenergic receptor subtypes in rat brain. Neuroscience 86:977–987CrossRefPubMedGoogle Scholar
  17. Hogg S (1996) A review of the validity and variability of the elevated plus-maze as an animal model of anxiety. Pharmacol Biochem Behav 54:21–30PubMedGoogle Scholar
  18. Jouvet D, Vimont P, Delorme F, Jouvet M (1964) Etude de la privation sélective de la phase paradoxale de sommeil chez le chat. C R Soc Biol (Paris) 158:756–759Google Scholar
  19. Koolhaas JM, Meerlo P, de Boer SF, Strubbe JH, Bohus B (1997) The temporal dynamics of the stress response. Neurosci Biobehav Rev 21:775–782PubMedGoogle Scholar
  20. Kushida CA, Bergmann BM, Rechtschaffen A (1989) Sleep deprivation in the rat. IV. Paradoxical sleep deprivation. Sleep 12:22–30PubMedGoogle Scholar
  21. Labatte LA, Johnson MR, Lydiard RB, Brawman-Mintzer O, Emmanuel N, Crawford M, Kapp R, Ballenger JC (1998) Sleep deprivation in social phobia and generalized anxiety disorder. Biol Psychiatry 43:840–842CrossRefPubMedGoogle Scholar
  22. Larsen JK, Lindberg ML, Skovgaard B (1976) Sleep deprivation as treatment for endogenous depression. Acta Psychiatr Scand 54:167–173PubMedGoogle Scholar
  23. Ledoux L, Sastre JP, Buda C, Luppi PH, Jouvet M (1996) Alterations in c-fos expression after different experimental procedures of sleep deprivation in the cat. Brain Res 735:108–118PubMedGoogle Scholar
  24. Lister RG (1987) The use of a plus-maze to measure anxiety in the mouse. Psychopharmacology 92:180–185PubMedGoogle Scholar
  25. Lourenzi VPM, Gabriel A Jr, Nunes G Jr, Atra E, Tufik S (1993) REM sleep deprivation and social isolation accelerate autoimmune disease in mice. Sleep Res 22:338Google Scholar
  26. Mendelson WB, Guthrie RD, Frederick G, Wyatt RJ (1974) The flower pot technique of rapid eye movement (REM) sleep deprivation. Pharmacol Biochem Behav 2:553–556Google Scholar
  27. Moser PC (1989) An evaluation of the elevated plus-maze test using the novel anxiolytic buspirone. Psychopharmacology 99:48–53PubMedGoogle Scholar
  28. Nunes GP, Tufik S (1994) Validation of the modified multiple platform method (MMP) of paradoxical sleep deprivation in rats. Sleep Res 22:339Google Scholar
  29. Patchev V, Felszeghy K, Korányi L (1991) Neuroendocrine and neurochemical consequences of a long-term sleep deprivation in rats: similarities to some features of depression. Homeostasis 33:97–108PubMedGoogle Scholar
  30. Peeke SC, Callaway E, Jones RT, Stone GC, Doyle J (1980) Combined effects of alcohol and sleep deprivation in normal young adults. Psychopharmacology 67:279–287PubMedGoogle Scholar
  31. Pellow S, Chopin P, File SE, Briley M (1985) Validation of open:closed arm entries in an elevated plus-maze as a measure of anxiety in the rats. J Neurosci Meth 14:149–167PubMedGoogle Scholar
  32. Pereira JK, Vieira RJ, Konishi CT, Ribeiro R de A, Frussa-Filho R (1999) The phenomenon of one-trial tolerance to the anxiolytic effect of chlordiazepoxide in the elevated plus maze is abolished by the introduction of a motivational conflict situation. Life Sci 65:101–107CrossRefGoogle Scholar
  33. Pokk P, Vali M (2001) Small platform stress increases exploratory activity of mice in staircase test. Prog Neuropsychopharmacol Biol Psychiatry 25:1435–1444CrossRefPubMedGoogle Scholar
  34. Pokk P, Zharkoversusky A (1995) The effects of drugs acting at GABA–benzodiazepine–barbiturate receptor complex on the behavior of sleep deprived mice. Pharmacol Toxicol 76:23–28PubMedGoogle Scholar
  35. Pokk P, Zharkoversusky A (1997) The effects of flumazenil, RO 15-4513 and β-CCM on the behaviour of control and stressed mice in the plus-maze test. J Physiol Pharmacol 48:253–261PubMedGoogle Scholar
  36. Pokk P, Zharkoversusky A (1998) Small platform stress attenuates the anxiogenic effect of diazepam withdrawal in the plus-maze test. Behav Brain Res 97:153–157CrossRefPubMedGoogle Scholar
  37. Pokk P, Liljequist S, Zharkoversusky A (1996) Ro 15-4513 potentiates, instead of antagonizes, ethanol-induced sleep in mice exposed to small platform stress. Eur J Pharmacol 317:15–20CrossRefPubMedGoogle Scholar
  38. Roy-Byrne PP, Uhde TW, Post RM (1986) Effects of one night’s sleep deprivation on mood and behavior in panic disorder. Arch Gen Psychiatry 43:895–899Google Scholar
  39. Seabra MLV, Tufik S (1993) Sodium diclofenac inhibits hyperthermia induced by paradoxical sleep deprivation: the possible participation of prostaglandins. Physiol Behav 54:923–926CrossRefPubMedGoogle Scholar
  40. Serra M, Pisu MG, Littera M, Papi G, Sanna E, Tuveri F, Usala L, Purdy RH, Biggio G (2000) Social isolation-induced decreases in both the abundance of neuroactive steroids and GABA(A) receptor function in rat brain. J Neurochem 75:732–740CrossRefPubMedGoogle Scholar
  41. Silva RH, Frussa-Filho R (2000) The plus-maze discriminative avoidance task: a new model memory–anxiety interactions. Effects of chlordiazepoxide and caffeine. J Neurosci Meth 102:117–125CrossRefPubMedGoogle Scholar
  42. Silva RH, Frussa-Filho R (2002) Naltrexone potentiates both amnestic and anxiolytic effects of chlordiazepoxide in mice. Life Sci 72:721–730CrossRefPubMedGoogle Scholar
  43. Silva RH, Kameda SR, Carvalho RC, Rigo GS, Costa KLB, Taricano ID, Frussa-Filho R (2002) Effects of amphetamine on the plus-maze discriminative avoidance task in mice. Psychopharmacology 160:9–18CrossRefPubMedGoogle Scholar
  44. Silva RH, Abílio VC, Takatsu AL, Kameda SR, Grassl C, Chehin AB, Medrano WA, Calzavara MB, Registro S, Andersen ML, Machado RB, Carvalho RC, Ribeiro R de A, Tufik S, Frussa-Filho R (2004) Role of hippocampal oxidative stress in memory deficits induced by sleep deprivation in mice. Neuropharmacology 46:895–903CrossRefPubMedGoogle Scholar
  45. Söderpalm B, Engel JÁ (1988) Biphasic effects of clonidine on conflict behavior: involvement of different alpha-adrenoceptors. Pharmacol Biochem Behav 30:471–477CrossRefPubMedGoogle Scholar
  46. Suchecki D, Tufik S (2000) Social stability attenuates the stress in the modified multiple platform method for paradoxical sleep deprivation in the rat. Physiol Behav 68:309–316CrossRefPubMedGoogle Scholar
  47. Suchecki D, Tiba PA, Tufik S (2002) Hormonal and behavioural responses of paradoxical sleep-deprived rats to the elevated plus-maze. J Neuroendocrinol 14:549–554CrossRefPubMedGoogle Scholar
  48. Svendsen K (1976) Sleep deprivation therapy in depression. Acta Psychiatr Scand 54:184–192PubMedGoogle Scholar
  49. Timo-Iaria C, Negrão N, Schmidek WR, Rocha TL, Hoshino K (1970) Phases and states of sleep in the rat. Physiol Behav 5:402–407Google Scholar
  50. Tufik S, Trocone LRP, Braz S, Silva-Filho AR, Neumann BG (1987) Does REM sleep deprivation induce subsensitivity of pre-synaptic dopamine of postsynaptic acetylcholine receptors in the brain? Eur J Pharmacol 140:215–219CrossRefPubMedGoogle Scholar
  51. Tufik S, Nathan CL, Neumann B, Hipólide DC, Lobo LL, Medeiros R, Trocone LRP, Braz S, Suchecki D (1995) Effects of stress on drug-induced yawning: constant versus intermittent stress. Physiol Behav 58:181–184CrossRefPubMedGoogle Scholar
  52. Van den Burg W, Van den Hoofdakker RH (1975) Total sleep deprivation on endogenous depression. Arch Gen Psychiatry 32:1121–1125PubMedGoogle Scholar
  53. Van Hulzen ZJM, Coenen AML (1981) Paradoxical sleep deprivation and locomotor activity in rats. Physiol Behav 27:741–744CrossRefPubMedGoogle Scholar
  54. Vovin RIA, Fakturovich AIA (1985) Sleep deprivation as a method of treating endogenous depression. Zh Nevropatol Psikhiatr Im S S Korsakova 85:560–565PubMedGoogle Scholar
  55. Wyatt RJ, Fram DH, Kupfer DJ, Snyder F (1971) Total prolonged drug-induced REM sleep suppression in anxious-depressed patients. Arch Gen Psychiatry 24:145–155PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Regina H. Silva
    • 1
  • Sonia R. Kameda
    • 1
  • Rita C. Carvalho
    • 1
  • André L. Takatsu-Coleman
    • 1
  • Suzy T. Niigaki
    • 1
  • Vanessa C. Abílio
    • 1
  • Sergio Tufik
    • 2
  • Roberto Frussa-Filho
    • 1
  1. 1.Departamento de FarmacolgiaUniversidade Federal de São PauloSao PauloBrazil
  2. 2.Departamento de PsicobiologiaUniversidade Federal de São PauloSao PauloBrazil

Personalised recommendations