Neonatal Excitotoxicity Triggers Degenerative Processes Related to Seizure Susceptibility and Pharmacoresistance

Neuronal damage and seizures are two closely related events, not only reciprocally as cause and effect but also through the cellular mechanisms and signaling pathways that they share throughout the degenerative processes that trigger them or are triggered by them. Therefore, increases in extracellular levels of the excitatory neurotransmitter glutamate, overactivation of its receptors, excessive neuronal excitation, and neuronal death by excitotoxicity have been described as part of these processes. Our group has shown that the excitotoxicity induced by monosodium glutamate (MSG) in the early stages of development produces significant modifications in the glutamatergic and GABAergic neurotransmission systems. In addition, an increased seizure susceptibility in adulthood has been observed after neonatal MSG treatment, particularly when the potassium channel blocker 4-aminopyridine or the gamma-aminobutyric acid (GABA) antagonist iodide-methyl-bicuculline is used as convulsive drugs, but not when the selective glutamate agonist N-methyl-d-aspartate (NMDA) is used. Throughout this chapter, the topics mentioned above and the hypothesis that neonatal excitotoxic damage can induce some type of drug resistance to NMDA analogs will be discussed in detail.