Development of EEG seizure activity during and after chronic ketamine administration in the rat

Abstract

Daily assessment of gross behavior and periodic EEG brain wave activity was performed in rats receiving daily ketamine administration for 1,2 and 3 months. Three groups were used for these studies; the first group received 80 mg kg ketamine intraperitoneally (i.p.), a dose which produces a cataleptoid-like behavior and characteristic EEG hypersynchronous patterns; the second group received 30 mg kg ketamine i.p. which induces behavioral excitation followed by ataxia and desynchronized EEG; the third group received saline control with no change in EEG or behavior noted. Abnormal spike and hypersynchronous bursting activity appeared in both the amygdala and dorsal hippocampus during the course of chronic administration of both the low and high dose of ketamine. The incidence of abnormal brain wave spiking was approximately 50% with 3 out of 5 animals demonstrating abnormal brain wave activity at the high dose and 1 out of 3 at the lower dose. During the course of the three months' administration of both the low and high dose of ketamine there was no evidence of tolerance or potentiation of the drug effect based on EEG or behavioral criteria. Withdrawal of the drug for 5 days following three months of treatment resulted in the appearance of a progressive increase in epileptiform activity without gross behavioral manifestations. The abnormal spike and slow wave EEG activity was not correlated with an observable abnormality in behavior.