Cholinergic agonist-antagonist interactions on neocortical and limbic EEG activation.

The effects of various cholinergic agonists and antagonists and their interactions were determined on the awake-sleep cycle of cats with chronic indwelling brain electrodes. The effects were measured by the use of the EEG and correlated with gross behavioral observation. EEG recordinxs were taken from various neocortical and limbic structures, ~cluding the amygdala and hi~pocampus. EEG activation and behavioral arousal following acetylcholine (0’007 mg/kg) intravenously was blocked by pretreatment with the muscarinic (m) choline& antagonists methyl atropine and atropine (@3 mg/kg). On the other hand this was not affected by the nicotinic (n) ganglionic cholin&ic antagonists trimethidinium (1 mg/kg) and mecamylamine (@7 mg/kp). EEG activation and behavioral arousal produced by arecoline (@4 mg/kg) was reduced slightly by methyl atropine and completely bl&ked by at&pine, but not modified by trimethidinium and mecamylamine. EEG activation and behavioral arousal produced by pilocarpine (O-15 mg/kg) was significantly reduced by methyl atropine and almost completely abolished by atropine. On the other hand, EEG activation produced by pilocarpine was not significantly blocked by the n choline@ antagonists. Pilocarpine caused a significant increase in the duration of fast wave sleep. It also produced an interesting phenomenon in which fast wave sleep frequently started from the resting state or followed a short drowsy period in contrast to its usual initiation from slow wave sleep. EEG activation and behavioral arousal were observed following physostigmine. These effects were reduced by methyl atropine and almost completely blocked by atropine. The n cholinergic antagonists did not show any significant effect on physostigmine-induced EEG activation and behavioral arousal. Fast wave sleep following physostigmine was also occasionally observed starting from the drowsy state. There was no increase in fast wave sleep in comparison to saline solution injection within 5’0 min following physostigmine. EEG activation and behavioral arousal were produced by nicotine (002 mg/kg). These effects were not altered significantly by methyl atropine, but moderately reduced by atropine. In addition, atropine produced a dissociation in which nicotine-induced EEG activation of the neocortex was still evident although hippocampal and amvndaloid activation were blocked. The EEG actions of nicotine were slightly reduced by tr~~~~idi~um and completely blocked by the admi~stration of mecamyl&ne. It is concluded that this study provides additional evidence for the role of m and n ganglionic cholinergic mechanisms in EEG activation of neocortical and limbic structures.