An analysis of mechanism of the appearance of convulsions after intraventricular injection of eserine

Abstract

The gross behavioural effects, especially clonic-tonic convulsions, caused by intraventricular injections of eserine were related to acetylcholinesterase inhibition. Eserine in a dose of 2.0 mg produced in the majority of experiments emotional, autonomic and motor phenomena with clonic-tonic convulsions. In a minority of experiments eserine in the same dose caused emotional, autonomic and motor changes without seizures. Eserine in the dose of 0.1 mg in all experiments produced emotional, autonomic and motor effects without clonictonic convulsions. The percentage of acetylcholinesterase inhibition in the superficial layers of caudate nucleus, thalamus and anterior part of hypothalamus did not differ significantly when eserine was applied in the dose of 0.1 mg and 2.0 mg not producing clonic-tonic convulsions. The enzyme inhibition was 2–5 times higher, except in the posterior part of hypothalamus, when eserine in the dose of 2.0 mg caused clonic-tonic convulsions. Thus, clonic-tonic convulsions occurred only after a certain degree of inhibition of acetylcholinesterase activity (caudate nucleus 61%, thalamus 33%, anterior hypothalamus 37% and posterior hypothalamus 40%), though the enzyme activity was not completely blocked. Apart from regional differences in the uptake of drugs injected intraventricularly, it is reasonable to suppose that a barrier exists between the cerebrospinal fluid and the brain tissue. The permeability of the barrier probably regulates the penetration of eserine into the brain tissue and so determines the degree of acetylcholinesterase inhibition and the appearance of the gross behavioural effects with or without clonic-tonic convulsions.