Amino acid influences on seizures elicited within the inferior colliculus

TJ McCown, BS Givens and GR Breese

Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill.

Using a model in which seizure activity was elicited electrically from the inferior colliculus, the influence of both inhibitory and excitatory putative neurotransmitter amino acids on this seizure activity was assessed by manipulating neurotransmitter amino acid function. It was found that i.c.v. administration of the inhibitory amino acids taurine (2.5 micrograms) or glycine (30 micrograms), or the gamma-aminobutyric acidA agonist, muscimol (300 ng), significantly elevated the threshold current necessary to initiate seizure activity from the inferior collicular cortex. Similarly, the microinjection of muscimol (10 or 30 ng) or racemic baclofen (20 or 60 ng), a gamma- aminobutyric acidB agonist, into the inferior collicular cortex significantly elevated the seizure threshold current, but inferior collicular microinjections of taurine (1 microgram) or glycine (1 microgram) exerted no effect on the seizure threshold current. When excitatory amino acid influences were assessed on seizure production, neither ventricular administration of glutamate or aspartate (100 micrograms) nor inferior collicular administration of glutamate (1 or 10 micrograms) or aspartate (10 micrograms) changed the seizure initiation threshold. Although the site administration of 30 or 100 ng of N-methyl-D-aspartic acid did not alter the seizure initiation threshold, 300 ng of N-methyl-D-aspartic acid significantly lowered the amount of electrical stimulation necessary to elicit the seizure activity. Conversely, blockade of N-methyl-D-aspartic acid receptors in the inferior colliculus with L-3-amino-7-phosphonoheptanoic acid (100 ng) or gamma-glutamylglycine (200 ng) significantly elevated the threshold current for seizure production, whereas microinjection of DL- 3-amino-phosphonobutyric acid (200 ng) or glutamic acid diethyl ester (1 microgram) had no effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 243, Issue 2, pp. 603-608, 11/01/1987
Copyright © 1987 by American Society for Pharmacology and Experimental Therapeutics