Convulsive seizures induced by α-amino-3-hydroxy-5-methyl-4-isoxazoleproplonic acid microinjection into the mesencephalic reticular formation in rats

Effects of microinjections of a single 2 or 10 nmol dose of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) into the unilateral mesencephalic reticular formation (MRF) on behavior and on the electroencephalogram were examined in rats (n=30) over a 15-min period (Exp. 1); subsequent effects of sound stimulation with key jingling applied at 15, 30, and 45 min after the injection were observed (Exp. 2). The microinjections of a 2 nmol dose of AMPA (n=15) induced hyperactivity (15 of 15 rats) and running/circling (10 of 15 rats) in Exp. 1, and hyperactivity (5 of 15 rats) in Exp. 2. Moreover, the microinjections of a 10 nmol dose of AMPA (n=15) induced hyperactivity (15 of 15 rats), running/circling (13 of 15 rats), generalized tonic-clonic seizures (GTCS) (4 of 15 rats), and amygdala kindling-like seizures (AMKS) (8 of 15 rats) in Exp. 1; electroencephalographic seizure discharges were predominantly observed in the MRF during hyperactivity, running/circling and GTCS, while those predominantly observed in the amygdala were during AMKS. To Exp. 2, hyperactivity (15 of 15 rats), running/circling (14 of 15 rats) and GTCS (6 of 15 rats) were elicited by sound stimulation, although AMKS were not. The control group of rats (n=15) which received a single dose of saline microinjection into the unilateral MRF showed no behavioral or electroencephalographic changes in both Exp. I and 2. These findings suggest that potentiation of excitatory amino acid neurotransmission induced by AMPA injection into the MRF plays an important role not only in the development of hyperactivity, running/circling, GTCS and AMKS, but also in the development of audiogenic seizures. (C) 2004 Elsevier B.V. All rights reserved.