Caloric restriction alters seizure disposition and behavioral profiles in seizure-prone (fast) versus seizure-resistant (slow) rats.

Abstract

Caloric restriction (CR), primarily known for extending life span, has proven anticonvulsant in several seizure models and antiepileptogenic in a strain of inherently seizure susceptible mice. Our animal model consisted of a seizure-prone (Fast) strain that naturally exhibits attention-deficit/hyperactivity disorder (ADHD)-like behaviors and a comparison seizure-resistant (Slow) strain; we evaluated CR's effect on the typical seizure sensitivities and behavioral profiles of each strain. Fast and Slow rats were fed ad libitum or were calorically restricted to 80% of free-feeding body weight. Rats were then tested in the open field (hyperactivity), Morris water maze (learning and attention), and restraint (impulsivity) paradigms and finally kindled from the amygdala. Ultimately, CR abolished signs of abnormal hyperactivity in the Fast strain and retarded their kindling rates, making it the first manipulation to demonstrate an antiepileptogenic effect in this animal model. CR also shortened seizure durations in fully kindled Slow rats but had no effect on their kindling rates, implying a differential effect of CR on genotype. These results clearly endorse further investigation into the potential benefits of CR for both epilepsy and ADHD.