The expression of
mRNA coding for
prepro-thyrotropin releasing hormone (preproTRH) was estimated in the rat brain in two animal models of limbic
seizures, evoked by systemic administration of
pilocarpine (400 mg/kg ip) or
kainate (12 mg/kg ip). As shown by an in situ hybridization study, after 24h both
pilocarpine- and
kainate-induced
seizures profoundly increased the preproTRH
mRNA level in the dentate gyrus. After 72h, the preproTRH
mRNA level was back to control values.
Kainate-treated rats showed an elevated level of TRH in the hippocampus, septum, frontal and occipital cortex after 24 and 72h, whereas in the striatum and amygdala the TRH level was raised after 72h only. In the hypothalamus, TRH levels was lowered after 3 and 24h, and returned to the control after 72h.
Pilocarpine-induced
seizures also elevated the TRH level after 72h in the majority of the above structures, except for the hypothalamus and amygdala where no changes were found at any time point. A radioreceptor assay showed that
kainate decreased the Bmax value of
TRH receptors in the striatum and hippocampus after 3 and 24h, respectively, and had no effect on the Kd values. In contrast,
pilocarpine-induced
seizures lowered the Bmax of
TRH receptors in the striatum, hippocampus and piriform cortex after 72h only, and decreased Kd values in the striatum, amygdala and frontal cortex. These data showed that
pilocarpine- and
kainate-induced
seizures enhanced likewise preproTRH
mRNA in the dentate gyrus; on the other hand, they differed with respect to time- and structure-related changes in TRH tissue levels and
TRH receptors. These differences may have functional significance in TRH-dependent control mechanism of the seizure activity in these two models of limbic
epilepsy.