Modafinil enhances thalamocortical activity by increasing neuronal electrotonic coupling.
Modafinil (Provigil, Modiodal), an antinarcoleptic and mood-enhancing drug, is shown here to sharpen thalamocortical activity and to increase electrical coupling between cortical interneurons and between nerve cells in the inferior olivary nucleus. After irreversible pharmacological block of connexin permeability (i.e., by using either 18beta-glycyrrhetinic derivatives or mefloquine), modafinil restored electrotonic coupling within 30 min. It was further established that this restoration is implemented through a Ca(2+)/calmodulin protein kinase II-dependent step.
Urbano
Francisco J
FJ
Department of Physiology and Neuroscience, New York University Medical Center, 550 First Avenue, New York, NY 10016, USA.
Leznik
Elena
E
Llinás
Rodolfo R
RR
D000818:Animals; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004583:Electrons; D004594:Electrophysiology; D051379:Mice; D000077408:Modafinil; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D013788:Thalamus / Q000187:drug effects / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D001559:Benzhydryl Compounds; D005680:gamma-Aminobutyric Acid; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D000077408:Modafinil