COMPARATIVE STUDY OF LACOSAMIDE, LAMOTRIGINE AND TOPIRAMATE TREATMENT ON PASSIVE LEARNING AND MEMORY IN NAÏVE RATS
Keywords:
Lacosamide, Lamotrigine, Topiramate, passive learning ad memoryAbstract
Epilepsy, as a socially significant disease affecting nearly 50 million people worldwide, is a neurological
disorder characterized by spontaneous recurrent seizures which impair patients' quality of life. Its pathogenesis and
development, as well as therapy with most of the drugs, lead to cognitive impairment. In the last decades, new
antiepileptic drugs (AEDs) such as lacosamide, lamotrigine, topiramate have been introduced. In addition to their
broad-spectrum therapeutic effects against different forms of epilepsy, some of them are considered significantly
rarer to lead to severe consequences on cognitive functions compared to the classic AEDs. The aim of the present
study was to investigate the effects of low doses of lacosamide, lamotrigine and topiramate on changes in passive
learning and memory in naïve animals. Material and methods: We used 32 male rats (Wistar) randomly divided into
4 groups (n = 8), as follows: 1st group – C-veh (treated with saline p.o.); 2nd group (LCM-group) – treated with
lacosamide 3 mg/kg p.o.; 3rd group (LTG-group) – treated with lamotrigine 5 mg/kg p.o. and the 4th group (TPMgroup)
– treated with topiramate 5 mg/kg p.o. 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 traces. The test for long-term memory traces in the step-through was performed on the 10th day.
The latency of reactions (the rat remaining in the light chamber of the device 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 during the learning session in the step-through test, the three groups treated with LCM, LTG, and TPM
had shorter the latency time compared to the control animals, without the difference being statistically significant.
On the 3rd and 10th day, during the tests for short-term and long-term memory traces, the three groups had similar
results to those of the control animals regarding their stay in the light chamber of the device. In the step-down
passive avoidance test, we found a significantly longer latency time of the control group on the 3rd (p<0.05) and 8th
(p<0.05) days compared to the first day of the same group. During the learning session, the three groups treated with
LCM, LTG, and TPM stayed longer on the platform compared to day 1 of the same group without the difference
being statistically significant. The LCM group had a longer latency time on day 1 compared to the control animals
(p<0.05). During both tests for short-term and long-term memory traces, the latency time of the three experimental
groups treated with the drugs were comparable to those of the control animals. Conclusion: The three drugs,
administered in low doses of 3 mg/kg for LCM and 5 mg/kg for lamotrigine and topiramate, did not affect
negatively both passive learning and the formation of short-term and long-term memory traces.
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