Modafinil increases arousal determined by P13 potential amplitude: an effect blocked by gap junction antagonists.
OBJECTIVE
We recorded the effects of administration of the stimulant modafinil on the amplitude of the sleep state-dependent auditory P13 evoked potential in freely moving rats, a measure of arousal thought to be generated by the cholinergic arm of the reticular activating system, specifically the pedunculopontine nucleus (PPN).


METHODS
Groups of rats were implanted for recording auditory evoked responses and the effects on P13 potential amplitude of intracranial injections into the PPN of neuroactive agents determined.


RESULTS
The effects of intracranial injections into the PPN of modafinil showed that P13 potential amplitude increased in a dose-dependent manner at doses of 100, 200, and 300 microM. The effect was blocked by pretreatment with either of the gap junction antagonists carbenoxolone (300 microM) or mefloquine (25 microM), which by themselves slightly decreased P13 potential amplitude.


CONCLUSIONS
These results suggest that modafinil increases arousal levels as determined by the amplitude of the P13 potential, an effect blocked by gap junction antagonists, suggesting that one mechanism by which modafinil increases arousal may be by increasing electrical coupling.
Beck
Paige
P
Center for Translational Neuroscience, Department of Neurobiology and Developmental Science, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Odle
Angela
A
Wallace-Huitt
Tiffany
T
Skinner
Robert D
RD
Garcia-Rill
Edgar
E
D000818:Animals; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D002229:Carbenoxolone / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D004569:Electroencephalography / Q000187:drug effects*; D005072:Evoked Potentials, Auditory / Q000187:drug effects*; D017629:Gap Junctions / Q000187:drug effects*; D007267:Injections; D008297:Male; D015767:Mefloquine / Q000494:pharmacology*; D000077408:Modafinil; D045042:Pedunculopontine Tegmental Nucleus / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000187:drug effects
D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D002229:Carbenoxolone; D000077408:Modafinil; D015767:Mefloquine