Immediate and delayed treatment with gabapentin, carbamazepine and CNQX have almost similar impact on cognitive functions and behavior in the lithium-pilocarpine model in rats

Abstract

In the present study, we aimed to investigate the effects of immediate and delayed treatment with intracerebroventricular (i.c.v.) gabapentin (GBP), carbamazepine (CBZ) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) on learning and memory, anxiety, and locomotor activity in rats with lithium-pilocarpine-induced status epilepticus (SE). SE was induced by intraperitoneal injections of 3 mEq/kg LiCl followed by 45 mg/kg pilocarpine 24 h later. In the first series of experiments, rats were divided into four groups three hours after the onset of SE and received GBP (100 mu g/10 mu l, two times a day; i.c.v.), CBZ (200 mu g/10 mu l; i.c.v.), CNQX (25 nmol/10 mu l; i.c.v.) or saline (10 mu l; i.c.v.) for 7 days. Six weeks after SE, cognitive and behavioral performances were evaluated by Morris water maze, elevated plus maze, and open field tests. In the second series, rats received no treatment for six weeks following SE. On the seventh week the same treatment with the previous rats was given and six weeks later the cognitive and behavioral tests were applied. SE significantly impaired spatial learning and memory in the Morris water maze. GBP treatment improved the acqusition and memory performance. CNQX worsened the acqusition but improved the memory performance, while CBZ worsened both parameters. In the elevated plus maze, epileptic rats which received saline showed significantly lower anxiety levels with respect to the naive rats. Only CBZ led to further anxiolysis, while the other drugs had no effect Locomotor activity significantly increased due to SE, which was augmented by GBP and CNQX. The impact of immediate and delayed treatment with these drugs on cognition and behavior seems to be quite similar.