Evidence that negative regulation of wakefulness in neonatal rats is an intrinsic function of the brain α2A-adrenergic receptors.
Previously, it was proposed that sedative and anesthetic effects of alpha2-adrenergic receptor (alpha2-AR) agonists may be exerted via neuronal networks normally implicated in the regulation of wakefulness. The aim of this study was to evaluate the role of A subtype of alpha2-ARs in the development of drug-independent anesthetic state induced by hypothermia in newborn rats. Using short interfering RNA (siRNA) gene-targeting strategy, we found that down-regulation of the brainstem alpha2A-AR expression resulted in a delay in the onset of hypothermia-induced anesthesia assessed by loss of righting reflex. Involvement of the brain alpha2A-ARs in this delay was confirmed by inability of clonidine, a subtype-nonselective alpha2-AR agonist, to prolong duration of hypothermia-induced anesthesia in siRNA-treated animals, while significant prolongation of this anesthetic state by the alpha2A-AR agonist was observed in control pups. The data suggest that negative regulation of the animal's waking state is an intrinsic function of the brainstem alpha2A-ARs activated by exogenous agonists, as well as by endogenous noradrenaline, also.
Dygalo
Nikolay N
NN
Functional Neurogenomics Laboratory, Institute of Cytology and Genetics, Lavrentjev av., 10, Novosibirsk 630090, Russia.
Kalinina
Tatjana S
TS
Shishkina
Galinat
G
D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001933:Brain Stem / Q000187:drug effects / Q000503:physiopathology*; D003000:Clonidine / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D009638:Norepinephrine / Q000502:physiology; D034622:RNA Interference / Q000502:physiology; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014474:Unconsciousness / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology*; D014851:Wakefulness / Q000187:drug effects / Q000235:genetics / Q000502:physiology*
D058647:Adrenergic alpha-2 Receptor Agonists; D034741:RNA, Small Interfering; D018341:Receptors, Adrenergic, alpha-2; D003000:Clonidine; D009638:Norepinephrine