Effect of thiopental sodium on N-methyl-D-aspartate-gated currents

Abstract

Purpose: N-methyl-D-aspartate (NMDA) receptors in the prefrontal cortex (PFC) are closely related with the excitability of pyramidal neurons and PFC function. As the effect of thiopental sodium on the central nervous system may partly result from the inhibition of PFC NMDA receptors, we investigated the effect of thiopental sodium with different concentrations on NMDA-gated currents in acutely dissociated rat PFC pyramidal neurons. We sought to determine whether thiopental sodium inhibits NMDA receptor function.Methods: Three to four week old male Sprague-Dawley rats were sacrificed and the PFC was dissected. Pyramidal neurons from the PFC were prepared and standard whole-cell patch clamp recordings were performed. Escalating concentrations from 3-1000 µM NMDA were applied 100 µm from the pyramidal cells, and the concentration in the effect compartment related to 50% effect (EC50) of NMDA was determined for the ensuing experiments. One hundred µM NMDA alone (control) or NMDA with different concentrations (10-1000 µM) of thiopental sodium were applied. After the inhibitory concentration, in 50% of NMDA effect (IC50) of thiopental sodium was established this IC50 and NMDA 3-1000 µM were applied 100 µm from the pyramidal cells. The EC50 value of NMDA under the effect of IC50 thiopental sodium was determined.Results: N-methyl-D-aspartate induced inward currents in a concentration-dependent manner, which were completely antagonized by 50 µM AP5. The maximal amplitude of NMDAinduced current was 1.15 ± 0.27 nA. The EC50 of NMDA was 53.6 ± 12.4 µM. The NMDA (100 µM)-gated current was inhibited by thiopental sodium in a concentration-dependent manner, and the IC50 of thiopental sodium was 33.6 ± 6.1 µM. Under the effect of 33.6 µM thiopental sodium, the maximal amplitude of NMDA-induced current was 0.87 ± 0.17 nA. The concentration-response curve of NMDA was shifted rightwards. The EC50 of NMDA was 128 ± 15 µM, which was greater than that of NMDA without thiopental sodium (P < 0.01). Conclusions:Thiopental sodium decreases NMDA-gated currents in acutely dissociated rat prefrontal cortical pyramidal neurons in a concentration-dependent manner. Objectif : Les récepteurs de N-méthyl-D-aspartate (NMDA) dans le cortex préfrontal (CPF) sont en lien étroit avec l'excitabilité des neurones pyramidaux et la fonction du CPF. L'effet du thio-

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