NMDA-dependent audiogenic seizures are differentially regulated by inferior colliculus subnuclei.
Wistar rats were classified as susceptible (S) and resistant (R) to audiogenic seizures (AS) by evaluation of their response to high intensity sound stimulation (110.3 dB). R rats usually do not respond with any convulsive behavior to sound stimulation, whereas S animals develop a complex wild running sequence plus tonic-clonic seizure patterns after sound stimulation. Thus, R rats were injected with phosphate buffer (PB; 0.2 microliter) or N-methyl-D-aspartate (NMDA) in three different doses (2.0 micrograms, 2.5 micrograms and 3.0 micrograms/0.2 microliter) into central ventral or cortical dorsal inferior colliculus (IC) nuclei. Dose-response curves were evaluated by means of an ethological method in which behavioral sequences typical of S and R animals were quantitated. Animals displayed more severe spontaneous audiogenic-like seizures with the dose of 2.5 micrograms/0.2 microliter NMDA, which were potentiated by the acoustic stimulus. Significant differences were apparent between central and cortical nuclei 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 micrograms NMDA microinjections into central or cortical nuclei. In S rats, AP7 totally blocked AS when microinjected into the central IC and partially, but significantly, blocked AS when applied into the cortical IC nucleus. In the last case, wild running was still present in 100% of the animals after AP7 treatment. These data may suggest an NMDA-dependent differential participation of IC subnuclei in the development of AS.
Terra
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VC
Department of Physiology, Ribeirão Preto School of Medicine, University of São Paulo, Brazil.
Garcia-Cairasco
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N
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives*; D000161:Acoustic Stimulation; D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001931:Brain Mapping; D004830:Epilepsy, Tonic-Clonic / Q000503:physiopathology; D007245:Inferior Colliculi / Q000187:drug effects / Q000503:physiopathology*; D016202:N-Methylaspartate / Q000494:pharmacology / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D051381:Rats; D012640:Seizures / Q000503:physiopathology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D000596:Amino Acids; D000927:Anticonvulsants; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; C031231:2-amino-7-phosphonoheptanoic acid