Ethosuximide Increases Exploratory Motivation and Improves Episodic Memory in the Novel Object Recognition Test in WAG/Rij Rats with Genetic Absence Epilepsy

Episodic memory was studied in WAG/Rij and Wistar rats aged 2 and 6 months in the novel object recognition test. WAG/Rij rats aged 6 months were given ethosuximide (300 mg/kg, 14 days, i.p.) to counter the symptoms of absence epilepsy and comorbid depression. The novel object recognition test consisted of the following phases: an adaptation phase, a familiarization phase (two identical objects), test phase 1 (a familiar object and an unfamiliar object), and test Phase 2 (a familiar object and an unfamiliar object). Exploratory activity (numbers of rearings and excursions to the center of the field) was recorded during the adaptation phase. Episodic memory was tested at 1 h (test phase 1) and 24 h (test phase 2) after the familiarization phase. Episodic memory was evaluated in terms of the index of recognition of the novel object. The novel object index of recognition was not significantly different in WAG/Rij rats from Wistar rats at age 2 months, but was significantly smaller than in Wistar rats at age 6 months. WAG/Rij rats displayed lower exploratory motivation than Wistar rats only at age 6 months. A positive correlation was seen between the index of recognition of the novel object and measures of exploratory motivation (number of rearings without support and number of excursions to the center of the field). Ethosuximide suppressed spike-wave activity, increased exploratory motivation, and improved episodic memory in WAG/Rij rats. The results provide evidence that impairments to episodic memory in the novel object recognition test in WAG/Rij rats may be due to decreased exploratory motivation as one of the symptoms of depression comorbid with absence epilepsy.