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GABA ergic transmission in rat pontine reticular formation regulates the induction phase of anesthesia and modulates hyperalgesia caused by sleep deprivation
Author(s) -
Vanini Giancarlo,
Nemanis Kriste,
Baghdoyan Helen A.,
Lydic Ralph
Publication year - 2014
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.12571
Subject(s) - propofol , chemistry , hyperalgesia , isoflurane , nociception , endocrinology , anesthetic , anesthesia , medicine , pharmacology , receptor
The oral part of the pontine reticular formation (PnO) contributes to the regulation of sleep, anesthesia and pain. The role of PnO γ‐aminobutyric acid ( GABA ) in modulating these states remains incompletely understood. The present study used time to loss and time to resumption of righting response (Lo RR and Ro RR ) as surrogate measures of loss and resumption of consciousness. This study tested three hypotheses: (i) pharmacologically manipulating GABA levels in rat PnO alters Lo RR , Ro RR and nociception; (ii) propofol decreases GABA levels in the PnO; and (iii) inhibiting GABA synthesis in the PnO blocks hyperalgesia caused by sleep deprivation. Administering a GABA synthesis inhibitor [3‐mercaptopropionic acid (3‐ MPA )] or a GABA uptake inhibitor [nipecotic acid ( NPA )] into rat PnO significantly altered Lo RR caused by propofol. 3‐ MPA significantly decreased Lo RR for propofol (−18%). NPA significantly increased Lo RR during administration of propofol (36%). Neither 3‐ MPA nor NPA altered Ro RR following cessation of propofol or isoflurane delivery. The finding that Lo RR was decreased by 3‐ MPA and increased by NPA is consistent with measures showing that extracellular GABA levels in the PnO were decreased (41%) by propofol. Thermal nociception was significantly decreased by 3‐ MPA and increased by NPA , and 3‐ MPA blocked the hyperalgesia caused by sleep deprivation. The results demonstrate that GABA levels in the PnO regulate the time for loss of consciousness caused by propofol, extend the concept that anesthetic induction and emergence are not inverse processes, and suggest that GABA ergic transmission in the PnO mediates hyperalgesia caused by sleep loss.