Thiocolchicoside (TCC) is used clinically for its muscle relaxant, anti-inflammatory, and analgesic properties. Our previous electrophysiological studies have indicated that TCC is a competitive antagonist of GABAARs, an action that results in a proconvulsant and convulsant activity in rats and humans. Recent preliminary evidence has suggested that pre-treatment of rats with lithium, at concentrations found in humans treated with lithium under clinical conditions, markedly enhances the convulsant effects of TCC. We thus aimed at evaluating the effects of the interaction between lithium and TCC on neuronal excitability in the rat dentate gyrus (DG). Hippocampal slices were incubated in the absence or presence of 1 mM LiCl for 6 h, and fEPSP were then recorded. LiCl incubation induced a significant increase of the I/O responses of fEPSPs compared to control conditions. Patch-clamp analysis in DG granule cells revealed that LiCl incubation enhanced the frequency of mEPSCs and reduced paired-pulse facilitation ratio suggesting that lithium increases the probability of glutamate release. Application of 1 uM TCC potentiated fEPSPs with a greater extent in slices incubated with LiCl compared with those with vehicle. These results indicate that treatment of slices with LiCl increases the excitatory postsynaptic responses in 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 some caution should be taken when such drug combination is used in clinical practice.
Lithium potentiates the effects of thiocolchicoside on neuronal excitability in rat dentate gyrus
OBILI, NICOLA;FRAU, ALDO;E. Sanna
2010-01-01
Abstract
Thiocolchicoside (TCC) is used clinically for its muscle relaxant, anti-inflammatory, and analgesic properties. Our previous electrophysiological studies have indicated that TCC is a competitive antagonist of GABAARs, an action that results in a proconvulsant and convulsant activity in rats and humans. Recent preliminary evidence has suggested that pre-treatment of rats with lithium, at concentrations found in humans treated with lithium under clinical conditions, markedly enhances the convulsant effects of TCC. We thus aimed at evaluating the effects of the interaction between lithium and TCC on neuronal excitability in the rat dentate gyrus (DG). Hippocampal slices were incubated in the absence or presence of 1 mM LiCl for 6 h, and fEPSP were then recorded. LiCl incubation induced a significant increase of the I/O responses of fEPSPs compared to control conditions. Patch-clamp analysis in DG granule cells revealed that LiCl incubation enhanced the frequency of mEPSCs and reduced paired-pulse facilitation ratio suggesting that lithium increases the probability of glutamate release. Application of 1 uM TCC potentiated fEPSPs with a greater extent in slices incubated with LiCl compared with those with vehicle. These results indicate that treatment of slices with LiCl increases the excitatory postsynaptic responses in 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 some caution should be taken when such drug combination is used in clinical practice.
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