NMDA-DEPENDENT AUDIOGENIC-SEIZURES ARE DIFFERENTIALLY REGULATED BY INFERIOR COLLICULUS SUBNUCLEI

Wistar rats were classified as susceptible (S) and resistant (R) to au diogenic seizures (AS) by evaluation of their response to high intensi ty sound stimulation (110.3 dB). R rats usually do not respond with an y convulsive behavior to sound stimulation, whereas S animals develop a complex wild running sequence plus tonic-clonic seizure patterns aft er sound stimulation. Thus, R rats were injected with phosphate buffer (PB; 0.2 mu l) or N-methyl-D-aspartate (NMDA) in three different dose s (2.0 mu g, 25 mu g and 3.0 mu g/0.2 mu l) into central ventral or co rtical dorsal inferior colliculus (IC) nuclei. Dose-response curves we re evaluated by means of an ethological method in which behavioral seq uences typical of S and R animals were quantitated. Animals displayed more severe spontaneous audiogenic-like seizures with the dose of 2.5 mu g/0.2 mu l NMDA, which were potentiated by the acoustic stimulus. S ignificant differences were apparent between central and cortical nucl ei and more severe seizures were observed in IC cortical microinjected animals. These audiogenic seizures were blocked with microinjections of 2-amino-7-phosphono-heptanoate (AP7) applied just before 2.5 mu g N MDA microinjections into central or cortical nuclei. In S rats, AP7 to tally blocked AS when microinjected into the central IC and partially, but significantly, blocked AS when applied into the cortical IC nucle us. In the last case, wild running was still present in 100% of the an imals after AP7 treatment. These data may suggest an NMDA-dependent di fferential participation of IC subnuclei in the development of AS.