NICOTINE-INDUCED EEG AND BEHAVIORAL AROUSAL*t

(-) Nicotine, in doses of OG%O~Ol mg/kg given intravenously over 1 min, produced transient behavioral arousal and EEG activation in cats with chronic indwelling brain electrodes. The effects of nicotine were evident when the animals were in natural slow wave (deep) sleep as observed behaviorally and by the EEG with recordings from various cortical and subcortical sites. After nicotine administration, the animals were aroused for a few minutes and later became sleepy behaviorally and showed EEG slow waves. This was frequently followed by activated or fast wave sleep. This phenomenon was not evident following infusion of equal volumes of warmed saline solution. In equal doses (+) nicotine, nicotine-N-oxide and cotinine did not affect EEG and behavior in slow wave sleeping cats. However, equipressor doses of (+) nicotine (0.05 mg/kg) and nicotine-N-oxide (1.5 mg/kg) produced slight behavioral and EEG arousal in cats with slow wave sleep. Massive doses of cotinine (2.5 mg/kg) given intravenously were less effective than (-) nicotine in doses of 0.01 mg/kg. Equipressor doses of epinephrine (E) (0402 mg/kg), phenylalanyl lysine vasopressin (50 milliunits/kg) and DMPP (04XtS mg/kg) produced weaker EEG activation and behavioral arousal than ( -) nicotine. Pretreatment with trimethidinium (2 mg/kg) prevented the cardiovascular effects of nicotine but did not alter greatly its behavioral arousal or EEG activation effects. On the other hand, mecamylamine (0.6 mg/kg) completely blocked the cardiovascular actions of nicotine as well as its effects on EEG and behavior. Larger doses of mecamylamine interfered with the natural sleep cycle of the cat. By use of such pharmacologic techniques it is concluded that the behavioral arousal and EEG desynchronizing effects of nicotine are due primarily to an action on the central nervous system rather than peripheral afferent stimulation or release of various neurohormones. However, these latter effects contribute to the total phenomenon produced by nicotine in intact animals.