Ibotenic acid: its excitatory and possibly sedative actions in cerebral cortex.

A slowly developing excitation with after discharge is produced by microiontophoretic application of the racemate of ibotenic acid to pericruciate cortical neurons of cats which had been "decerebrated" by forebrain isolation during brief anesthesia. The extracellular observed excitation tended to accumulate with repeated applications. In many instances the ibotenate excitation was blocked with local administration of H2-receptor antagonists which also "'antagonized" glutamate excitation. With intracellular recording, similar iontophoretic applications of ibotenate were observed to produce longlasting depolarizations and repetitive firing which was not maintained despite suprathreshold depolarization. These actions were not accompanied by consistent changes in membrane resistance. A most striking feature of ibotenate action was to increase spontaneous synaptic activity and the amplitude of EPSP's evoked by electrical stimulation of the cortical surface or n. ventralis lateralis of the thalamus. These new data are strongly suggestive of presynaptic actions of ibotenate in the cerebral cortex although postsynaptic actions of this isoxazole presumably are also important to an understanding of how ibotenate produces its inebriating and hypnotic effects in animals and man.