EFFECT OF TOPIRAMATE TREATMENT ON PASSIVE COGNITIVE FUNCTIONS AND LOCOMOTOR ACTIVITY IN A MODEL OF DRUG-INDUCED AMNESIA
Keywords:
Topiramate, Diazepam, learning, memory, step-through, step-downAbstract
Introduction: Epilepsy is a chronic neurological disorder which can affects negatively behavior and
cognition. On the other hand, most antiepileptic drugs (AEDs) can also further impair cognitive functions.
Benzodiazepines are widely used in experimental models to induce cognitive deficits. Topiramate (TPM) exerts its
antiepileptic effects by several mechanisms of action and it is widely used in clinical practice. The aim of the present
study was to investigate the effect of topiramate on cognitive functions and locomotor activity in a model of
diazepam (DZP)-induced amnesia. Material and methods: We used 24 male adult rats (Wistar), which were
randomly divided into 3 groups (n = 8), as follows: 1st group - control (treated with saline p.o.); 2nd group (DZPveh)–
treated with saline p.o. and Diazepam 2.5 mg/kg i.p. and the 3rd group (DZP-TPM) – treated with topiramate 5
mg/kg p.o. and DZP 2.5 mg/kg i.p. In the test for locomotor activity (Activity cage), the number of horizontal and
vertical movements was recorded. In the two passive avoidance tests (step-through and step-down), the training
session was conducted on two consecutive days. 24 hours after the last learning session was the test for short-term
memory. The test for long-term memory in the Step-through was performed on the 10th day. The latency of reactions
(the rat remaining in the light chamber of the apparatus for more than 178 sec in 2 consecutive training sessions)
was considered as a criterion for acquisition and retention. In the step-down test, the long-term memory was tested
on the 8th day. The latency of reactions (the rat remaining on the platform for more than 60 sec in 2 consecutive
training sessions) was taken as a criterion for acquisition and retention. Results: One-way ANOVA showed that both
groups DZP-veh and DZP-TPM decreased the number of horizontal movements compared to the controls on day 7
(p < 0.001, resp.) and day 14 (p < 0.001, p < 0.05, resp.). In the step-through test, the DZP-veh group had a shorter
latency time than that of the C-veh animals in the short-term memory retention test (p < 0.01), while in the longterm
memory retention test, both groups DZP-veh and DZP-TPM (p < 0.05, resp.) had a shorter latency time and
spent less time in the light chamber of the device. In the step-down passive avoidance test, the DZP-veh group
shortened the latency time compared to the controls during the learning session on day 2 (p < 0.001). In the short -
term- and long-term memory tests, both groups DZP-veh (p < 0.001) and DZP-TPM (p < 0.05) spent less time on
the platform compared to the control animals. Conclusion: Topiramate failed to counteract the cognitive deficit
induced by diazepam administration, leading to impaired formation of short-term and long-term memory traces.
Topiramate failed to restore the suppressed locomotor activity. The AED did not have a negative effect on learning
abilities.
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