Hypocretin and GABA interact in the pontine reticular formation to increase wakefulness

Holly N. Brevig, Christopher J. Watson, Ralph Lydic, Helen Baghdoyan

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Study Objectives: Hypocretin-1/orexin A administered directly into the oral part of rat pontine reticular formation (PnO) causes an increase in wakefulness and extracellular γ-aminobutyric acid (GABA) levels. The receptors in the PnO that mediate these effects have not been identified. Therefore, this study tested the hypothesis that the increase in wakefulness caused by administration of hypocretin-1 into the PnO occurs via activation of GABAA receptors and hypocretin receptors. Design: Within/between subjects. Setting: University of Michigan. Patients or Participants: Twenty-three adult male Crl:CD*(SD) (Sprague Dawley) rats. Interventions: Microinjection of hypocretin-1, bicuculline (GABAA receptor antagonist), SB-334867 (hypocretin receptor-1 antagonist), and Ringer solution (vehicle control) into the PnO. Measurements and Results: Hypocretin-1 caused a significant concentration- dependent increase in wakefulness and decrease in rapid eye movement (REM) sleep and non-REM (NREM) sleep. Coadministration of SB-334867 and hypocretin-1 blocked the hypocretin-1-induced increase in wakefulness and decrease in both the NREM and REM phases of sleep. Coadministration of bicuculline and hypocretin-1 blocked the hypocretin-1-induced increase in wakefulness and decrease in NREM sleep caused by hypocretin-1. Conclusion: The increase in wakefulness caused by administering hypocretin-1 to the PnO is mediated by hypocretin receptors and GABAA receptors in the PnO. These results show for the first time that hypocretinergic and GABAergic transmission in the PnO can interact to promote wakefulness.

Original languageEnglish (US)
Pages (from-to)1285-1293
Number of pages9
JournalSleep
Volume33
Issue number10
DOIs
StatePublished - Oct 1 2010
Externally publishedYes

Fingerprint

Wakefulness
gamma-Aminobutyric Acid
Orexin Receptors
Sleep
Bicuculline
REM Sleep
GABA-A Receptors
Orexins
Pontine Tegmentum
Aminobutyrates
GABA-A Receptor Antagonists
Microinjections
Eye Movements
Sprague Dawley Rats

All Science Journal Classification (ASJC) codes

  • Clinical Neurology
  • Physiology (medical)

Cite this

Hypocretin and GABA interact in the pontine reticular formation to increase wakefulness. / Brevig, Holly N.; Watson, Christopher J.; Lydic, Ralph; Baghdoyan, Helen.

In: Sleep, Vol. 33, No. 10, 01.10.2010, p. 1285-1293.

Research output: Contribution to journalArticle

Brevig, Holly N. ; Watson, Christopher J. ; Lydic, Ralph ; Baghdoyan, Helen. / Hypocretin and GABA interact in the pontine reticular formation to increase wakefulness. In: Sleep. 2010 ; Vol. 33, No. 10. pp. 1285-1293.
@article{b5e40ec327e04b529ecf563357b46257,
title = "Hypocretin and GABA interact in the pontine reticular formation to increase wakefulness",
abstract = "Study Objectives: Hypocretin-1/orexin A administered directly into the oral part of rat pontine reticular formation (PnO) causes an increase in wakefulness and extracellular γ-aminobutyric acid (GABA) levels. The receptors in the PnO that mediate these effects have not been identified. Therefore, this study tested the hypothesis that the increase in wakefulness caused by administration of hypocretin-1 into the PnO occurs via activation of GABAA receptors and hypocretin receptors. Design: Within/between subjects. Setting: University of Michigan. Patients or Participants: Twenty-three adult male Crl:CD*(SD) (Sprague Dawley) rats. Interventions: Microinjection of hypocretin-1, bicuculline (GABAA receptor antagonist), SB-334867 (hypocretin receptor-1 antagonist), and Ringer solution (vehicle control) into the PnO. Measurements and Results: Hypocretin-1 caused a significant concentration- dependent increase in wakefulness and decrease in rapid eye movement (REM) sleep and non-REM (NREM) sleep. Coadministration of SB-334867 and hypocretin-1 blocked the hypocretin-1-induced increase in wakefulness and decrease in both the NREM and REM phases of sleep. Coadministration of bicuculline and hypocretin-1 blocked the hypocretin-1-induced increase in wakefulness and decrease in NREM sleep caused by hypocretin-1. Conclusion: The increase in wakefulness caused by administering hypocretin-1 to the PnO is mediated by hypocretin receptors and GABAA receptors in the PnO. These results show for the first time that hypocretinergic and GABAergic transmission in the PnO can interact to promote wakefulness.",
author = "Brevig, {Holly N.} and Watson, {Christopher J.} and Ralph Lydic and Helen Baghdoyan",
year = "2010",
month = "10",
day = "1",
doi = "10.1093/sleep/33.10.1285",
language = "English (US)",
volume = "33",
pages = "1285--1293",
journal = "Sleep",
issn = "0161-8105",
publisher = "American Academy of Sleep Medicine",
number = "10",

}

TY - JOUR

T1 - Hypocretin and GABA interact in the pontine reticular formation to increase wakefulness

AU - Brevig, Holly N.

AU - Watson, Christopher J.

AU - Lydic, Ralph

AU - Baghdoyan, Helen

PY - 2010/10/1

Y1 - 2010/10/1

N2 - Study Objectives: Hypocretin-1/orexin A administered directly into the oral part of rat pontine reticular formation (PnO) causes an increase in wakefulness and extracellular γ-aminobutyric acid (GABA) levels. The receptors in the PnO that mediate these effects have not been identified. Therefore, this study tested the hypothesis that the increase in wakefulness caused by administration of hypocretin-1 into the PnO occurs via activation of GABAA receptors and hypocretin receptors. Design: Within/between subjects. Setting: University of Michigan. Patients or Participants: Twenty-three adult male Crl:CD*(SD) (Sprague Dawley) rats. Interventions: Microinjection of hypocretin-1, bicuculline (GABAA receptor antagonist), SB-334867 (hypocretin receptor-1 antagonist), and Ringer solution (vehicle control) into the PnO. Measurements and Results: Hypocretin-1 caused a significant concentration- dependent increase in wakefulness and decrease in rapid eye movement (REM) sleep and non-REM (NREM) sleep. Coadministration of SB-334867 and hypocretin-1 blocked the hypocretin-1-induced increase in wakefulness and decrease in both the NREM and REM phases of sleep. Coadministration of bicuculline and hypocretin-1 blocked the hypocretin-1-induced increase in wakefulness and decrease in NREM sleep caused by hypocretin-1. Conclusion: The increase in wakefulness caused by administering hypocretin-1 to the PnO is mediated by hypocretin receptors and GABAA receptors in the PnO. These results show for the first time that hypocretinergic and GABAergic transmission in the PnO can interact to promote wakefulness.

AB - Study Objectives: Hypocretin-1/orexin A administered directly into the oral part of rat pontine reticular formation (PnO) causes an increase in wakefulness and extracellular γ-aminobutyric acid (GABA) levels. The receptors in the PnO that mediate these effects have not been identified. Therefore, this study tested the hypothesis that the increase in wakefulness caused by administration of hypocretin-1 into the PnO occurs via activation of GABAA receptors and hypocretin receptors. Design: Within/between subjects. Setting: University of Michigan. Patients or Participants: Twenty-three adult male Crl:CD*(SD) (Sprague Dawley) rats. Interventions: Microinjection of hypocretin-1, bicuculline (GABAA receptor antagonist), SB-334867 (hypocretin receptor-1 antagonist), and Ringer solution (vehicle control) into the PnO. Measurements and Results: Hypocretin-1 caused a significant concentration- dependent increase in wakefulness and decrease in rapid eye movement (REM) sleep and non-REM (NREM) sleep. Coadministration of SB-334867 and hypocretin-1 blocked the hypocretin-1-induced increase in wakefulness and decrease in both the NREM and REM phases of sleep. Coadministration of bicuculline and hypocretin-1 blocked the hypocretin-1-induced increase in wakefulness and decrease in NREM sleep caused by hypocretin-1. Conclusion: The increase in wakefulness caused by administering hypocretin-1 to the PnO is mediated by hypocretin receptors and GABAA receptors in the PnO. These results show for the first time that hypocretinergic and GABAergic transmission in the PnO can interact to promote wakefulness.

UR - http://www.scopus.com/inward/record.url?scp=77956856103&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77956856103&partnerID=8YFLogxK

U2 - 10.1093/sleep/33.10.1285

DO - 10.1093/sleep/33.10.1285

M3 - Article

VL - 33

SP - 1285

EP - 1293

JO - Sleep

JF - Sleep

SN - 0161-8105

IS - 10

ER -