Long-term increase in striatal thyrotropin-releasing hormone receptor binding caused by amygdaloid kindling.

Abstract

Our previous finding that intracerebroventricular (i.c.v.) administration of both thyrotropin-releasing hormone (TRH) and its analogue, gamma-butyrolactone-gamma-carbonyl-L-histidyl-L-prolinamide citrate (DN-1417), suppressed seizure development of amygdaloid (AM) kindling and kindled AM seizures leads to a new hypothesis that endogenous TRH may be an antiepileptic substance in the brain. In this study, we examined postictal chronological changes in both immunoreactive TRH (IR-TRH) and TRH receptor binding activity in discrete brain regions of AM-kindled rats to study the relationship of the brain TRH system to kindling-induced seizure susceptibility. AM-kindled rats were decapitated 30 min, 24 h, 48 h, 7 days, and 21 days after the last kindled convulsion. IR-TRH increased markedly in the AM/pyriform cortex and hippocampus 24 and 48 h after the last convulsion, and returned to the control (unstimulated, sham-operated) value within 3 weeks after the convulsions ended. In contrast, a significant increase in the striatal TRH binding sites was evident 24 h after the cessation of convulsions which lasted 21 days. A lasting change in the striatal TRH neural system may be related to kindling-induced seizure susceptibility.