Effects of sodium valproate on synaptic plasticity in the CA1 region of rat hippocampus

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 investgate 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) GABAA receptor antagonist picrotoxin (PTX) (10 μM) 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 γ-aminobutyric acid (GABA) receptor.