Seizures and thyrotropin-releasing hormone (TRH) neural system in the rat brain

In order to study the relationship between seizures and the thyrotropin-releasing hormone (TRH) neural system, immunoreactive TRH (IR-TRH) and TRH receptor binding activity were determined by pentylenetetrazol (PTZ)-induced seizures and amygdaloid (AM) kindling. IR-TRH markedly increased in the septum 40 and 150 seconds after the PTZ injection. A significant increase in the IR-TRH concentrations was also noted in the hippocampus and thalamus/midbrain 40 and 150 seconds after the PTZ injection, respectively. However, no significant changes were observed in the TRH receptor binding before, during or after the PTZ-induced seizures. In addition, a lasting change in the striatal TRH receptors after AM kindling as well as a transient IR-TRH increase in the limbic structures were seen 48 hours after Am-kindled convulsions. TRH and its analog (DN-1417) inhibited PTZ-induced generalized seizures dose-dependently. These findings indicate the involvement of the TRH neural system in seizure mechanisms, and suggest that endogenous TRH may be an antiepileptic substance in the brain.