Modafinil increases arousal determined by P13 potential amplitude: an effect blocked by gap junction antagonists.

Study Objectives: 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).

Design: 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.

Measurements And 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.