Changes in learning and memory, acetylcholinesterase activity and monoamines in brain after chronic carbamazepine administration in rats.

Abstract

Groups of adult male Wistar rats were administered carbamazepine (CBZ) in doses of 5, 10, 20, 40 or 80 mg/kg/day intraperitoneally (i.p.) for 21 days. The learning and memory of the rats were assessed by the T-maze and passive avoidance tests. The CBZ plasma levels, the activity of acetylcholinesterase (AChE) in different brain regions, and the levels of monoamines in the hippocampus were also measured. None of the administered doses of CBZ impaired learning and memory. Rats with CBZ plasma levels of 2.5 and 4.5 micrograms/ml corresponding to the doses of 20 and 40 mg/kg, learned significantly better than controls. AChE activity was decreased in hippocampus and pyriform cortex (19%) in these groups. Simultaneously, an increase in the serotonin (5-HT) (36%) and dopamine (137%) levels in the hippocampus was noted in the 20-mg/kg CBZ group. 5-Hydroxyindole acetic acid (5-HIAA) and homovanillic acid (HVA) levels were increased at 10-, 20-, and 40-mg/kg CBZ doses. However, a dose of 80-mg/kg caused no change in learning performance as compared with that of controls. Correspondingly, no changes were evident in the AChE activity or monoamine levels. We postulated that the decreased AChE activity caused by CBZ in the therapeutic range may lead to increased ACh levels in brain, thus producing improvement in learning and memory. The increased turnover of 5-HT and dopamine (DA) in the hippocampus may play a role in long-term potentiation and improvement in memory.