Effects of pilocarpine- and kainate-induced seizures on thyrotropin-releasing hormone biosynthesis and receptors in the rat brain

The expression of mRNA coding for prepro-thyrotropin releasing hormone (pre proTRH) was estimated in the rat brain in two animal models of limbic seizu res, evoked by systemic administration of pilocarpine (400mg/kg ip) or kain ate (12mg/kg ip). As shown by an in situ hybridization study, after 24h bot h pilocarpine- and kainate-induced seizures profoundly increased the prepro TRH mRNA level in the dentate gyrus. After 72h, the preproTRH mRNA level wa s back to control values. Kainate-treated rats showed an elevated level of TRH in the hippocampus, septum, frontal and occipital cortex after 24 and 7 2h, 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 ret urned 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 poin t. A radioreceptor assay showed that kainate decreased the B-max value of T RH receptors in the striatum and hippocampus after 3 and 24h, respectively, and had no effect on the K-d values. In contrast, pilocarpine-induced seiz ures lowered the B-max of TRH receptors in the striatum, hippocampus and pi riform cortex after 72h only, and decreased K-d values in the striatum, amy gdala and frontal cortex. These data showed that pilocarpine- and kainate-i nduced seizures enhanced likewise preproTRH mRNA in the dentate gyrus; on t he other hand, they differed with respect to time- and structure-related ch anges in TRH tissue levels and TRH receptors. These differences may have fu nctional significance in TRH-dependent control mechanism of the seizure act ivity in these two models of limbic epilepsy.