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Article Abstract
Sodium valproate (VPA) is currently one of the major anticonvulsant drug in clinical use and has a wide spectrum of antiepileptic activity. Previous studies have reported that VPA impairs long-term potentiation (LTP). In the present study, we used two forms of synaptic plasticity, LTP and long-term depression (LTD) of field excitatory postsynaptic potential (fEPSP) to investigate the effects of VPA on synaptic plasticity in rat hippocampal slices. Paired-pulse facilitation (PPF) and field EPSP were recorded in the CA1 area of hippocampal slices exposed to VPA. The results showed that: (1) three different concentrations of VPA (0.6, 1 and 5 mM) all induced a significant impairment of PPF at 20-150 ms inter-pulse intervals (IPI) (P<0.05). (2) acute VPA exposure (0.6 mM) inhibited the induction of LTP (Control: 171 +/- 20%, n=8; VPA-exposed: 117 +/- 16%, n=9, P<0.01) and LTD (Control: 86 +/- 13%, n=8; VPA-exposed: 98 +/- 8%, n=10, P<0.01); and (3) GABA(A) receptor antagonist picrotoxin (PTX) (10 microM) reversed VPA-induced deficits of LTP (VPA-exposed: 117 +/- 16%, n=9; VPA-exposed+PTX: 153 +/- 20%, n=8, P<0.01). However, PTX had no significant effect on impairment of LTD (VPA-exposed: 98 +/- 8%, n=10; VPA-exposed+PTX: 97 +/- 3%, n=8, P>0.05). These results suggested that VPA impaired LTP and LTD. Furthermore, VPA-induced impairment of LTP could be correlated with the enhancement of inhibitory neurotransmission mediated by gamma-aminobutyric acid (GABA) receptor.
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