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 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.
Zhang
Min-Min
MM
School of Life Science, University of Science and Technology of China, Hefei, Anhui, 230027, PR China.
Xiao
Cheng
C
Yu
Kuai
K
Ruan
Di-Yun
DY
D000818:Animals; D000927:Anticonvulsants / Q000633:toxicity*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects*; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000187:drug effects*; D014635:Valproic Acid / Q000037:antagonists & inhibitors / Q000633:toxicity*
D000927:Anticonvulsants; D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D010852:Picrotoxin; D014635:Valproic Acid