| Abstrakt: |
The WAG/Rij rat strain is a valid model of absence epilepsy with comorbid depression. Absence epilepsy, along with symptoms of depression, is known to be associated with cognitive impairments, such as deficits in attention and cognitive flexibility, with the latter being a major indicator of executive functions. The aim of the present study was to find out whether there are cognitive flexibility impairments in WAG/Rij rats and whether they are associated with absence epilepsy and comorbid depression. To reveal the differences in cognitive flexibility, acquisition learning (direct task) and reversal learning (reversal task) in the complex maze with food reinforcement were compared in WAG/Rij rats aged 2 months, when symptoms of absence epilepsy and comorbid depression are absent, and 6 months, when the pathologic phenotype is fully expressed. Food motivation was assessed in the novelty-suppressed feeding (NSF) test. Wistar rats were used as a control. Ethosuximide (ETX, 300 mg/kg/day, 17 days) was used to suppress symptoms of absence epilepsy and depression-like comorbidity in WAG/Rij rats. It was found that at the age of 6 months, WAG/Rij rats performed acquisition and reversal learning tasks more slowly, made more errors, and exhibited reduced food motivation in the NSF test (longer latency to approach food in an unfamiliar open field, and the smaller amount of food consumed in the home cage) compared to Wistar rats. At the age of 2 months, WAG/Rij rats did not differ from Wistar rats in any of the indicators. ETX improved reversal learning, decreased the number of errors, and increased food motivation in 6-months-old WAG/Rij rats. In Wistar rats, ETX exerted no significant effects on reversal learning. In 6-month-old WAG/Rij rats, a positive correlation (r = 0.66; p < 0.05) was found between the amount of food consumed in the home cage (a food motivation measure) and the rate of achieving the learning criterion when executing the reversal task (a cognitive flexibility measure). Our results suggest that the cognitive flexibility impairments revealed in WAG/Rij rats may be a consequence of reduced food motivation as one of the symptoms of depression comorbid to absence epilepsy. [ABSTRACT FROM AUTHOR] |
