Enriched environment attenuates behavioral seizures and depression in chronic temporal lobe epilepsy.

Objective: Temporal lobe epilepsy (TLE) is commonly associated with depression, anxiety, and cognitive impairment. Despite significant progress in our understanding of the pathophysiology of TLE, it remains the most common form of refractory epilepsy. Enriched environment (EE) has a beneficial effect in many neuropsychiatric disorders. However, the effect of EE on cognitive changes in chronic TLE has not been evaluated. Accordingly, the present study evaluated the effects of EE on chronic epilepsy-induced alterations in cognitive functions, electrophysiology, and cellular changes in the hippocampus.

Methods: Status epilepticus (SE) was induced in 2-month-old male Wistar rats with lithium and pilocarpine. Six weeks' post SE, epileptic rats were either housed in their respective home cages or in an enrichment cage (6 h/day) for 14 days. Seizure behavior was video-monitored 2 weeks before and during exposure to EE. Depression-like behavior, anxiety-like behavior, and spatial learning and memory were assessed using the sucrose preference test (SPT), elevated plus maze (EPM), and Morris water maze (MWM), respectively. Delta and theta power in the CA1 region of hippocampus was assessed from recordings of local field potentials (LFPs). Cellular changes in hippocampus were assessed by histochemistry followed by unbiased stereologic analysis.

Results: EE significantly reduced seizure episodes and seizure duration in epileptic rats. In addition, EE alleviated depression and hyperactivity, and restored delta and theta power of LFP in the hippocampal CA1 region. However, EE neither ameliorated epilepsy-induced spatial learning and memory deficits nor restored cell density in hippocampus.

Significance: This is the first study that evaluates the role of EE in a chronic TLE model, where rats were exposed to EE after occurrence of spontaneous recurrent seizures (SRS). Given that 30% of TLE patients are refractory to drug treatment, therapeutic strategies that utilize components of EE could be designed to alleviate seizures and psychiatric comorbidities associated with TLE.