Dexmedetomidine-induced sedation does not mimic the neurobehavioral phenotypes of sleep in sprague dawley rat

Abigail G. Garrity, Simhadri Botta, Stephanie B. Lazar, Erin Swor, Giancarlo Vanini, Helen Baghdoyan, Ralph Lydic

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Study Objectives: Dexmedetomidine is used clinically to induce states of sedation that have been described as homologous to nonrapid eye movement (NREM) sleep. A better understanding of the similarities and differences between NREM sleep and dexmedetomidine-induced sedation is essential for efforts to clarify the relationship between these two states. This study tested the hypothesis that dexmedetomidine-induced sedation is homologous to sleep.

Design: This study used between-groups and within-groups designs.

Setting: University of Michigan.

Participants: Adult male Sprague Dawley rats (n = 40).

Interventions: Independent variables were administration of dexmedetomidine and saline or Ringer's solution (control). Dependent variables included time spent in states of wakefulness, sleep, and sedation, electroencephalographic (EEG) power, adenosine levels in the substantia innominata (SI), and activation of pCREB and c-Fos in sleep related forebrain regions.

Measurements and Results: Dexmedetomidine significantly decreased time spent in wakefulness (-49%), increased duration of sedation (1995%), increased EEG delta power (546%), and eliminated the rapid eye movement (REM) phase of sleep for 16 h. Sedation was followed by a rebound increase in NREM and REM sleep. Systemically administered dexmedetomidine significantly decreased (-39%) SI adenosine levels. Dialysis delivery of dexmedetomidine into SI did not decrease adenosine levels. Systemic delivery of dexmedetomidine did not alter c-Fos or pCREB expression in the horizontal diagonal band, or ventrolateral, median, and medial preoptic areas of the hypothalamus.

Conclusions: Dexmedetomidine significantly altered normal sleep phenotypes, and the dexmedetomidine-induced state did not compensate for sleep need. Thus, in the Sprague Dawley rat, dexmedetomidine-induced sedation is characterized by behavioral, electrographic, and immunohistochemical phenotypes that are distinctly different from similar measures obtained during sleep.

Original languageEnglish (US)
Pages (from-to)73-84
Number of pages12
JournalSleep
Volume38
Issue number1
DOIs
StatePublished - Jan 1 2015

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Dexmedetomidine
Sprague Dawley Rats
Sleep
Phenotype
Substantia Innominata
Eye Movements
Adenosine
Wakefulness
REM Sleep
Preoptic Area
Prosencephalon
Sodium Chloride
Hypothalamus
Dialysis

All Science Journal Classification (ASJC) codes

  • Clinical Neurology
  • Physiology (medical)

Cite this

Dexmedetomidine-induced sedation does not mimic the neurobehavioral phenotypes of sleep in sprague dawley rat. / Garrity, Abigail G.; Botta, Simhadri; Lazar, Stephanie B.; Swor, Erin; Vanini, Giancarlo; Baghdoyan, Helen; Lydic, Ralph.

In: Sleep, Vol. 38, No. 1, 01.01.2015, p. 73-84.

Research output: Contribution to journalArticle

Garrity, Abigail G. ; Botta, Simhadri ; Lazar, Stephanie B. ; Swor, Erin ; Vanini, Giancarlo ; Baghdoyan, Helen ; Lydic, Ralph. / Dexmedetomidine-induced sedation does not mimic the neurobehavioral phenotypes of sleep in sprague dawley rat. In: Sleep. 2015 ; Vol. 38, No. 1. pp. 73-84.
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abstract = "Study Objectives: Dexmedetomidine is used clinically to induce states of sedation that have been described as homologous to nonrapid eye movement (NREM) sleep. A better understanding of the similarities and differences between NREM sleep and dexmedetomidine-induced sedation is essential for efforts to clarify the relationship between these two states. This study tested the hypothesis that dexmedetomidine-induced sedation is homologous to sleep.Design: This study used between-groups and within-groups designs.Setting: University of Michigan.Participants: Adult male Sprague Dawley rats (n = 40).Interventions: Independent variables were administration of dexmedetomidine and saline or Ringer's solution (control). Dependent variables included time spent in states of wakefulness, sleep, and sedation, electroencephalographic (EEG) power, adenosine levels in the substantia innominata (SI), and activation of pCREB and c-Fos in sleep related forebrain regions.Measurements and Results: Dexmedetomidine significantly decreased time spent in wakefulness (-49{\%}), increased duration of sedation (1995{\%}), increased EEG delta power (546{\%}), and eliminated the rapid eye movement (REM) phase of sleep for 16 h. Sedation was followed by a rebound increase in NREM and REM sleep. Systemically administered dexmedetomidine significantly decreased (-39{\%}) SI adenosine levels. Dialysis delivery of dexmedetomidine into SI did not decrease adenosine levels. Systemic delivery of dexmedetomidine did not alter c-Fos or pCREB expression in the horizontal diagonal band, or ventrolateral, median, and medial preoptic areas of the hypothalamus.Conclusions: Dexmedetomidine significantly altered normal sleep phenotypes, and the dexmedetomidine-induced state did not compensate for sleep need. Thus, in the Sprague Dawley rat, dexmedetomidine-induced sedation is characterized by behavioral, electrographic, and immunohistochemical phenotypes that are distinctly different from similar measures obtained during sleep.",
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T1 - Dexmedetomidine-induced sedation does not mimic the neurobehavioral phenotypes of sleep in sprague dawley rat

AU - Garrity, Abigail G.

AU - Botta, Simhadri

AU - Lazar, Stephanie B.

AU - Swor, Erin

AU - Vanini, Giancarlo

AU - Baghdoyan, Helen

AU - Lydic, Ralph

PY - 2015/1/1

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N2 - Study Objectives: Dexmedetomidine is used clinically to induce states of sedation that have been described as homologous to nonrapid eye movement (NREM) sleep. A better understanding of the similarities and differences between NREM sleep and dexmedetomidine-induced sedation is essential for efforts to clarify the relationship between these two states. This study tested the hypothesis that dexmedetomidine-induced sedation is homologous to sleep.Design: This study used between-groups and within-groups designs.Setting: University of Michigan.Participants: Adult male Sprague Dawley rats (n = 40).Interventions: Independent variables were administration of dexmedetomidine and saline or Ringer's solution (control). Dependent variables included time spent in states of wakefulness, sleep, and sedation, electroencephalographic (EEG) power, adenosine levels in the substantia innominata (SI), and activation of pCREB and c-Fos in sleep related forebrain regions.Measurements and Results: Dexmedetomidine significantly decreased time spent in wakefulness (-49%), increased duration of sedation (1995%), increased EEG delta power (546%), and eliminated the rapid eye movement (REM) phase of sleep for 16 h. Sedation was followed by a rebound increase in NREM and REM sleep. Systemically administered dexmedetomidine significantly decreased (-39%) SI adenosine levels. Dialysis delivery of dexmedetomidine into SI did not decrease adenosine levels. Systemic delivery of dexmedetomidine did not alter c-Fos or pCREB expression in the horizontal diagonal band, or ventrolateral, median, and medial preoptic areas of the hypothalamus.Conclusions: Dexmedetomidine significantly altered normal sleep phenotypes, and the dexmedetomidine-induced state did not compensate for sleep need. Thus, in the Sprague Dawley rat, dexmedetomidine-induced sedation is characterized by behavioral, electrographic, and immunohistochemical phenotypes that are distinctly different from similar measures obtained during sleep.

AB - Study Objectives: Dexmedetomidine is used clinically to induce states of sedation that have been described as homologous to nonrapid eye movement (NREM) sleep. A better understanding of the similarities and differences between NREM sleep and dexmedetomidine-induced sedation is essential for efforts to clarify the relationship between these two states. This study tested the hypothesis that dexmedetomidine-induced sedation is homologous to sleep.Design: This study used between-groups and within-groups designs.Setting: University of Michigan.Participants: Adult male Sprague Dawley rats (n = 40).Interventions: Independent variables were administration of dexmedetomidine and saline or Ringer's solution (control). Dependent variables included time spent in states of wakefulness, sleep, and sedation, electroencephalographic (EEG) power, adenosine levels in the substantia innominata (SI), and activation of pCREB and c-Fos in sleep related forebrain regions.Measurements and Results: Dexmedetomidine significantly decreased time spent in wakefulness (-49%), increased duration of sedation (1995%), increased EEG delta power (546%), and eliminated the rapid eye movement (REM) phase of sleep for 16 h. Sedation was followed by a rebound increase in NREM and REM sleep. Systemically administered dexmedetomidine significantly decreased (-39%) SI adenosine levels. Dialysis delivery of dexmedetomidine into SI did not decrease adenosine levels. Systemic delivery of dexmedetomidine did not alter c-Fos or pCREB expression in the horizontal diagonal band, or ventrolateral, median, and medial preoptic areas of the hypothalamus.Conclusions: Dexmedetomidine significantly altered normal sleep phenotypes, and the dexmedetomidine-induced state did not compensate for sleep need. Thus, in the Sprague Dawley rat, dexmedetomidine-induced sedation is characterized by behavioral, electrographic, and immunohistochemical phenotypes that are distinctly different from similar measures obtained during sleep.

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