Early-life hyperthermic seizures upregulate adenosine A2A receptors in the cortex and promote depressive-like behavior in adult rats

Abstract

Febrile seizures (FS) represent one of the most frequent convulsive disorders in children which can be classified into simple and prolonged depending on the duration. Although simple FS are generally considered as benign, there is controversy about the outcome of prolonged FS. Here, we have used an animal model of prolonged FS to investigate persistent neurochemical and behavioral alterations in adult rats. Hyperthermic seizures were induced in 12-day-old rats using a warmed air stream from a hair dryer. Neonates exhibited arrest of heat-induced hyperkinesis followed by body flexion and rearing and falling over associated with hindlimb clonus seizures (stage 5 on Racine scale criteria) after hyperthermic induction. After 48 days, the animals were assayed on dark–light box and forced swim tests in order to detect if rats will show signs of anxiety or depression. Finally, animals were sacrificed 56 days after hyperthermia-induced seizures (HIS), and their effects on adenosine A2A receptor signaling and 5′-nucleotidase activity were studied in plasma membranes from the cerebral cortex by using radioligand-binding assay and by measuring the activities of adenylate cyclase and 5′-nucleotidase. Results obtained have shown that adult rats submitted to HIS during the neonatal period showed depressive-like behavior. Furthermore, animals exposed to hyperthermic insult showed an increase in A2A receptor level which was also accompanied by an increase in A2A receptor functionality.