Alpha2C-adrenoceptor mediated regulation of cortical EEG arousal

Abstract

Alpha2-adrenergic drugs modulate cortical arousal and EEG. However, the role of individual alpha2-adrenoceptor ( α 2-AR) subtypes in these functions is not clear. We investigated the role of α 2C-ARs in the modulation of baseline cortical EEG activity and EEG responses to the α 2-AR selective agonist, dexmedetomidine (3–300 μg/kg, s.c.), and antagonist, atipamezole (3-1000 μg/kg, s.c.), by using α 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 μg/kg) more effectively slowed and atipamezole (30-1000 μg/kg) less effectively increased cortical EEG arousal in KO mice compared to WT controls. Importantly, autoradiographical results showed no compensatory increase in other α 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 α 2-AR selective drugs in KO mice indicate that α 2C-ARs are involved in regulation of cortical arousal. These results suggest that α 2C-ARs may antagonize the sedative effect of α 2-AR agonists mediated by activation of α 2A-ARs.