LITHIUM AND THIOCOLCHICOSIDE INTERACTION ON RAT DENTATE GYRUS NEURONAL NETWORK EXCITABILITY

Obili N;Fadda E.;Uras R.;Cordeddu G.;Fois C.;Prinzis S.;FRAU, ALDO;Piras V.;Siuni L.;Niola P.;De Riu PL;Sechi GP;Sanna E.

2010-01-01

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Abstract

The muscle relaxant thiocolchicoside (TCC) is commonly used in clinical practice also for its anti-inflammatory and analgesic effects. Several previous studies have proposed that TCC as a competitive antagonist of GABAARs, and in vivo exerts a proconvulsant and convulsant activity in rats and humans. Preliminary data suggest that pre treatment of rats with concentration of lithium similar to those found in humans under clinical conditions, markedly enhances the convulsant effects of TCC. To better understand the nature of the interaction between lithium and TCC, we performed extracellular electrophysiological recordings of fEPSPs and evaluated the neuronal excitability in rat dentate gyrus (DG) slices. After 6 h of LiCl (1 mM) incubation the I/O responses of fEPSPs were markedly enhanced compared to control. Application of 1 M TCC potentiated fEPSPs with a greater efficacy in slices after LiCl incubation. Patch-clamp recordings in DG granule cells revealed that LiCl incubation enhanced the frequency of mEPSCs and reduced paired-pulse facilitation ratio suggesting an increased probability of glutamate release. Taken together these results indicate that treatment of slices with LiCl increases fEPSP recorded from DG granule cells, and markedly potentiates the effects of TCC. The strong increase of DG neuronal excitability induced by the association of lithium and TCC is consistent with the pharmacological observation of an enhanced convulsant activity in rats and suggests that particular attention should be taken when such drug combination is used in clinical practice.