Sodium salicylate enhances neural excitation via reducing GABAergic transmission in the dentate gyrus area of rat hippocampus in vivo

Abstract

Sodium salicylate, one of the non‐steroidal anti‐inflammatory drugs, is widely prescribed in the clinic, but a high dose of usage can cause hyperactivity in the central nervous system, including the hippocampus. At present, the neural mechanism underlying the induced hyperactivity is not fully understood, in particular, in the hippocampus under an in vivo condition. In this study, we found that systemic administration of sodium salicylate increased the field excitatory postsynaptic potential slope and the population spike amplitude in a dose‐dependent manner in the hippocampal dentate gyrus area of rats with in vivo field potential extracellular recordings, which indicates that sodium salicylate enhances basal synaptic transmission and neural excitation. In the presence of picrotoxin, a GABA‐A receptor antagonist, sodium salicylate failed to increase the initial slope of the field excitatory postsynaptic potential and the amplitude of the population spike in vivo. To further explore how sodium salicylate enhances the neural excitation, we made whole‐cell patch‐clamp recordings from hippocampal slices. We found that perfusion of the slice with sodium salicylate decreased electrically evoked GABA receptor‐mediated currents, increased paired‐pulse ratio, and lowered frequency and amplitude of miniature inhibitory postsynaptic currents. Together, these results demonstrate that sodium salicylate enhances the neural excitation through suppressing GABAergic synaptic transmission in presynaptic and postsynaptic mechanisms in the hippocampal dentate gyrus area. Our findings may help understand the side effects caused by sodium salicylate in the central nervous system.

Long-term maintenance of synaptic plasticity by Fullerenol Ameliorates lead-induced-impaired learning and memory in vivo

“…In order to explore the possible mechanism of fullerenol in protecting hippocampus from being injured by lead, in vivo extracellular field potential recording has been used in our study. Unlike in vitro intracellular electrophysiology recording, it may be more truly and completely reflect the efficacy of drugs, through some important indicators such as I/O function, PPF ratio and LTP [ 27 , 28 ]. Two major pathways into and out of the hippocampus (the PP-DG pathway and the SCh-CA1 pathway), coordinately maintain synaptic transmission in hippocampus and are suitable to verify the possible effect of synaptic plasticity in the process of fullerenol against lead-induced injury [ 29 – 31 ].…”

Salicylate Induced GABAAR Internalization by Dopamine D1-Like Receptors Involving Protein Kinase C (PKC) in Spiral Ganglion Neurons

“…SS can cause neuronal excitotoxicity by inhibiting GABA A R function [ 10 , 23 ], but the molecular mechanism is not fully understood. Research showed that the cochlear response of the D1 knockout mice was enhanced, and the auditory brainstem response (ABR) threshold of all frequencies was increased by 5–20 dB [ 12 ], indicating that D1Rs play an important role in auditory function.…”