Hypocretin and GABA interact in the pontine reticular formation to increase wakefulness.
Sleep
; 33(10): 1285-93, 2010 Oct.
Article
in En
| MEDLINE
| ID: mdl-21061850
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 gamma-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 ORPARTICIPANTS:
Twenty-three adult male CrlCD*(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 ANDRESULTS:
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Reticular Formation
/
Wakefulness
/
Neuropeptides
/
Pons
/
Receptors, GABA-A
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Intracellular Signaling Peptides and Proteins
/
Gamma-Aminobutyric Acid
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
Sleep
Year:
2010
Document type:
Article
Affiliation country:
United States