Effect of atropine and eserine on the episodic behavioral and electrographic manifestations induced by methionine sulfoximine

Abstract

The effects of eserine and atropine on the sound-induced episodic behavioral manifestations were examined in sixteen cats and forty rats treated with methionine sulfoximine (MSI). Behaviorally, eserine markedly increased the frequency of sound-induced fright behavior and episodic running (ERB) with or without associated convulsion in cats, and of ERB in rats. Atropine markedly reduced the frequency of sound-induced ERB in both cats and rats but increased generalized convulsions only in cats. Electrographically, both auditory stimulation and eserine produced low-voltage irregular fast EEG patterns in MSI-treated cats. No organized electrographic seizure discharge was observed during ERB but was noted during the stuporous cataleptic state following ERB in one cat. There was no depression of electrical activity following ERB or of the electrographic seizure following ERB. Atropine produced a high voltage irregular slow EEG pattern, which was not modified by auditory stimulation. The generalized convulsions developed only when the EEG pattern was of high voltage slow activity. It began with focal spike discharge in the amygdala and in the hippocampus or pyriform cortex, or both, correlated with facial twitching which built up into an organized seizure with progressive propagation into widespread brain areas coincident with generalized convulsion. There was a profound post-ictal electrographic depression. These findings further strengthen our view that ERB in both MSI-treated cats or rats and genetically-determined audiogenic sensitive rats is an identical phenomenon. In addition, it is suggested that ERB is coincident with excitation, and the generalized convulsion is coincident with blocking of the cholinergic mechanism involved in the ascending neuronal transmission of the brain stem reticular system.