Interstrain differences in cognitive functions in rats in relation to status epilepticus

Abstract

Cognitive functions of Long Evans ( N=30) and Wistar rats ( N=32) were compared using a Morris water maze. Under control conditions the Long Evans rats were more efficient in this test, their average escape latency after 5 days of training (6.4±0.1 s, mean±S.E.M.) was significantly shorter than that of the Wistar rats (11.0±0.1 s). When the training was completed seizures were induced by an intraperitoneal injection of pilocarpine (330 mg/kg in the Long Evans strain and 350 mg/kg in the Wistar rats) 30 min after pretreatment with N-methylscopolamine (1 mg/kg i.p.). Clonazepam (1 mg/kg i.p.) was used to interrupt clonic seizures after 2 hours of continuous activity. Approximately one quarter of rats in both strains did not develop seizures. Severe convulsive status epilepticus was common in Long Evans rats (23 out of 30). In contrast, only 12 Wistar rats generated convulsive status epilepticus and the same number of animals exhibited only bursts of motor seizures separated by periods without convulsions (temporary seizures). Mortality after pilocarpine-induced status epilepticus was considerably higher in the Long Evans rats than in the Wistar rats. After a latency of 2–3 weeks spontaneous recurrent seizures appeared in all animals surviving status. Cognitive memory was tested during the ‘silent period’ between status and recurrent seizures. The Long Evans rats were unable to find the platform at the 3rd and 6th day after status but then their performance rapidly improved. The performance of the Wistar rats undergoing status epilepticus was seriously deteriorated and it never normalized, whereas the animals with temporary seizures exhibited only a transitory marginal prolongation of latencies. The hippocampal formation was damaged by status epilepticus in rats of both strains — the Long Evans rats exhibited more extensive damage of subfields CA1 and CA3, whereas in the Wistar rats a complete destruction of hilar neurons was observed in addition to partial CA1 and CA3 damage.