J Korean Child Neurol Soc.  2005 Nov;13(2):128-136.

The Effects of Lamotrigine on Epileptiform Discharges Induced by Mg2+ -free Medium and 4-aminopyridine in Hippocampal Slices of Immature Rats

• Yoon JS
• Lee IG
• Choi BJ
• Whang KT

Abstract

PURPOSE
In order to elucidate the actual mechanism and the optimal concentration of Lamotrigine(LTG) that suppresses epileptiform discharges, we observed epileptiform discharges from hippocampal slices of immature rat in 4-aminopyridine(4-AP) added Mg2+ - free medium of artificial cerebrospinal fluid(aCSF) with various LTG concentrations.
METHODS
We divided 19-23 day-old Sprague-Dawley rats into 4 groups; control group(n=12) and 3 LTG groups depending on the concentrations of LTG such as 400 (n=9), 800(n=7), and 1,000(n=8) microM. The rats were anesthetized and their brains were taken, soaked in aCSF(NaCl 125 mM, KCl 2.5 mM, NaH2PO4 2 mM, MgSO4 1.25 mM NaHCO3 25 mM, CaCl2 2 mM, Glucose 10 mM, pH 7.3-7.4). And then the brains were cut into 400 microm hippocampal slices by a vibratome. The slices of control group were soaked in 200 microM 4-AP added Mg2+ -free medium of aCSF for 1 hour, and then extracellular recordings were performed in hippocampal CA1 pyramidal region. The slices of LTG groups were soaked in the solution containing 400, 800, and 1,000 microM LTG, then extracellular recordings were performed.
RESULTS
Interictal discharges were observed in all the control and the LTG groups. The latency to the first interictal discharges after 4-AP addition was 52.7+/-26.9 sec in control group, but was 225.0+/-28.2 sec in 800 microM and 322.1+/-116.4 sec in 1,000 microM group of LTG(P<0.05). The duration of interictal discharges was 64.6+/-35.6 sec in control group, but was the shortest in 800 microM group of LTG at 39.3+/-12.6 sec. Ictal discharges were observed in all of control and 400 microM group, but the frequency was decreased as the concentration of LTG increases, 57.1% in 800 microM, 12.5% in 1,000 microM group. The latency to ictal discharge after 4-AP addition was 142.1+/-52.6 sec in control group, but increased as the concentration of LTG increases, 304.4+/-84.5 sec in 400 microM group and 689.8+/-213.1 sec in 800 microM group(P<0.05). The duration of ictal discharges was 1,534.7/-339.3 sec in control group, but decreased as the concentration of LTG increases, it was 126.5+/-76.1 sec in 800 microM group(P <0.05) and 42 sec in 1,000 microM group.
CONCLUSION
The antiepileptic effects of LTG were most significant when the concentration, inhibiting epileptiform discharges induced by 4-AP and Mg2+ -free medium in hippocampal slices of immature rats, was 800 microM or higher. Although the basic pharmacologic mechanism of LTG is the inhibition of sodium channel, it may also work on potassium channel at higher concentrations.

Keyword

Lamotrigine; Mg2+-free medium; 4-aminopyridine; Interictal discharge; Ictal discharge

MeSH Terms

4-Aminopyridine*
Animals
Brain
Glucose
Hydrogen-Ion Concentration
Potassium Channels
Rats*
Rats, Sprague-Dawley
Sodium Channels
4-Aminopyridine
Glucose
Potassium Channels
Sodium Channels