Alpha2C-adrenoceptor mediated regulation of cortical EEG arousal

Alpha2-adrenergic drugs modulate cortical arousal and EEG. However, the role of individual alpha2-adrenoceptor (alpha(2)-AR) sub-types 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 alpha2-AR selective agonist, dexmedetomidine (3-300 mug/kg, s.c.), and antagonist, atiparnezole (3-1000 mug/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 mug/kg) more effectively slowed and atiparnezole (30-1000 mug/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. (C) 2002 Elsevier Science Ltd. All rights reserved.