Thyrotropin releasing hormone (TRH) systems have been implicated in the modulation of seizure activity. Induction of seizures by electroconvulsive shock, kindling or systemic administration of kaninic acid results in pronounced increases in the concentration of TRH in limbic CNS regions, hippocampus, amygdala/piriform cortex, anterior and posterior cortices. TRH and TRH analogs were shown to exert anticonvulsive activity following either peripheral or central administration. The goal of this proposal is to further explore the role of TRH systems in seizure activity. The effect of prolonged limbic seizure activity or kindling on TRH biosynthesis will be determined utilizing in situ hybridization methods to detect changes in TRH prohormone mRNA expression. The effect of seizure activity on specific populations of TRH receptors in the hippocampus, amygdala/piriform cortex and entorhinal cortex prior to initiation of seizures. The results of these studies will provide information necessary to evaluate the potential utility of the use of TRH or TRH analogs as a component of the management of epilepsy.
