title: Alpha 2C-adrenoceptor mediated regulation of cortical EEG arousal.
abstract: Alpha2-adrenergic drugs modulate cortical arousal and EEG. However, the role of individual alpha2-adrenoceptor (alpha(2)-AR) subtypes in these functions is not clear. We investigated the role of alpha(2C)-ARs in the modulation of baseline cortical EEG activity and EEG responses to the alpha(2)-AR selective agonist, dexmedetomidine (3-300 microg/kg, s.c.), and antagonist, atipamezole (3-1000 microg/kg, s.c.), by using alpha(2C)-AR knockout (KO) and wildtype (WT) mice. The overall amplitude (1-30 Hz) was not significantly altered in KO mice although the activity of theta band (4-8 Hz) was increased in these mice. The main finding was that dexmedetomidine (30-300 microg/kg) more effectively slowed and atipamezole (30-1000 microg/kg) less effectively increased cortical EEG arousal in KO mice compared to WT controls. Importantly, autoradiographical results showed no compensatory increase in other alpha(2)-AR subtypes in cortical, thalamic or other brain structures of KO mice. Furthermore, there were no differences between the genotypes in the levels of hippocampal choline acetyltransferase, monoamines or their metabolites. Altered baseline cortical EEG activity and EEG responses to alpha(2)-AR selective drugs in KO mice indicate that alpha(2C)-ARs are involved in regulation of cortical arousal. These results suggest that alpha(2C)-ARs may antagonize the sedative effect of alpha(2)-AR agonists mediated by activation of alpha(2A)-ARs.
authors.affiliation: Department of Neuroscience and Neurology, University of Kuopio, Kuopio University Hospital, P.O. Box 1627, FIN-70211, Kuopio, Finland. Jukka.Puolivali@uku.fi
authors.forename: Jukka
authors.initials: J
authors.lastname: Puoliväli
authors.forename: Markus
authors.initials: M
authors.lastname: Björklund
authors.forename: Maya
authors.initials: M
authors.lastname: Holmberg
authors.forename: Jouni A
authors.initials: JA
authors.lastname: Ihalainen
authors.forename: Mika
authors.initials: M
authors.lastname: Scheinin
authors.forename: Heikki
authors.initials: H
authors.lastname: Tanila
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000818:Animals; D001143:Arousal / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D020927:Dexmedetomidine / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000187:drug effects; D005260:Female; D007093:Imidazoles / Q000008:administration & dosage; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018341:Receptors, Adrenergic, alpha-2 / Q000172:deficiency* / Q000235:genetics
chemical_list: C547775:Adra2c protein, mouse; D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D007093:Imidazoles; D018341:Receptors, Adrenergic, alpha-2; C050701:atipamezole; D020927:Dexmedetomidine