DC Potential Shifts Associated With Convulsive Seizures and Brain Monoamine Changes in Rabbits

Abstract

SUMMARYRecordings were made of changes in the cerebral direct current potential (DC potential) as well as in polygraphic patterns occurring in association with convulsive seizures, various kinds of stimuli, sleep and brain amine changes in some 50 rabbits. Careful scrutiny of tracings thus obtained led to the following conclusions: The cortical and caudate DC potentials showed a negative shift of approximately 2 mV in conjunction with convulsive seizures induced by 25 mg/kg bemegride. A similar DC shift was observable during seizures provoked by pentetrazol or brain damage, These negative DC shifts were more rapid and of greater magnitude in the cerebral cortex than in the caudate nucleus. Stimulation with sound as well as with flash light gave rise to a negative shift of the cortical DC potential, with a habi‐tuation to these sensory stimuli of evoked DC potential changes being observed. Pen‐tobarbital‐induced sleep as well as spontaneous sleep shifted the caudate and cortical DC potentials to positivity, the response being more rapid and greater in magnitude in the caudate nucleus. The subcutaneous administration of 25–50 mg/kg L‐SHTP was followed by a negative shift (2–2.5 mV) of both the caudate and cortical DC potentials, whereas a 100–200 mg/kg subcutaneous dose of L‐DOPA was accompanied by a shift to positivity (1.0–1.5 mV) of the DC potential evoked in these brain areas. When administered by intraventricular injection, 100–200 pg serotonin caused a negative DC shift of 3–4 mV, while 100–200 μg dopamine and 200–300 μg noradrenaline were associated with a positive DC shift (approximately 1 mV and 1–2 mV, respectively). The latency of these responses was longer with precursors than with amines, being 30 minutes with L‐SHTP and 10 minutes with serotonin as well as 30 minutes with L‐DOPA, 15 minutes with dop‐amine and 5 minutes with noradrenaline. These figures suggest that the observed changes in DC potential are a phenomenon which is correlated with the metabolic process of biogenic amines. With the substance of the catecholamine series, a polygraphic pattern of slight waking reaction type with a concomitant increase in motor activity was observed in association with a positive DC shift. By contrast, a polygraphic pattern characteristic of sleep was seen with serotonin in conjunction with a negative DC shift, and motor activity tended to be diminished both with L‐SHTP and serotonin. While the administration of L‐DOPA in rabbits was followed by a tendency toward depressed amplitude of deep EEG activity, a dose of L‐5HTP or serotonin (intraventricular) was accompanied by convulsive seizures in some cases. In all two of two cases pretreated with MAOI, the administration of L‐SHTP was associated with the appearance of seizure discharges and, in one of them, even with fatal convulsions. In an epileptic patient who was on an oral antiepileptic medication, the oral administration of 100 mg L‐SHTP resulted in an elevation of serum serotonin level with concurrent activation of seizure discharges and the subsequent use of 200 mg L‐DOPA proved effective in antagonizing this activating action of L‐5HTP. In experimental epilepsy of rabbits, L‐DOPA exhibited an inhibitory action on kindled convulsion, but L‐SHTP had an equivocal effect of activating seizure activity. The results of OUT present study suggest that convulsive seizures, sensory stimulation, decreased cerebral levels of cate‐cholamines and increased levels of indole amines are associated with a negative cerebral DC potential shift, while suppressed convulsions, sleep, elevated cerebral levels of catecholamines and lowered levels of indole amines are accompanied by a positive DC potential shift.