NR2B receptor antagonist Ro25-6981 inhibits newborn neuron induced long-term potentiation in the dentate gyrus of adult rats*,☆

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Newborn neurons have been shown to induce long-term potentiation (LTP). Activation of N-methyl-D-aspartic acid (NMDA) receptor subunit NR2B plays an important role in mature neurons-induced LTP. But there have been no reports addressing on the effects of NR2B activation on newborn neuron-induced LTP.


To investigate the effects of NR2B receptor antagonist Ro25-6981 on LTP induced by newborn neurons in adult rat dentate gyrus.


An electrophysiological recording trial was performed at the Department of Neurobiology, Shanxi Medical University from February to June 2007.


Twenty-six male Wistar rats, aged 3 months, were provided by Laboratory Animal Center, Shanxi Medical University.


Following sacrifice for brain harvesting under anesthesia, the hippocampus was taken to preparation of 400 μ mol/L brain slices. Using extracellular field potential recordings, low-frequency stimulation was performed in the medial molecular layer of dentate gyrus with insulated bipolar tungsten electrodes. After having stable recordings, LTP was induced under high-frequency tetanic stimulation. LTP was induced with a protocol developed previously (4 trains, 500 ms each, 100 Hz within the train, repeated every 20 s). Only those slices which produced the field excitatory postsynaptic potential of 1 mV or higher in amplitude were accepted for further experiments. ①NR2B receptor antagonist Ro25-6981 blocked artificial cerebrospinal fluid (ACSF)-induced LTP (ACSF-LTP): brain slices were divided into 2 groups: ACSF group, in which, slices were continuously perfused using ACSF bubbled with 95% O2 and 5% CO2; ACSF+ Ro25-6981 group: a 10-minute treatment with 3 μ mol/L Ro25-6981 was performed prior to tetanic stimulation, and the remaining procedures were the same as ACSF group. ② NR2B receptor antagonist Ro25-6981 inhibited bicuculline (BIC)-induced LTP (BIC-LTP): brain slices were also divided into 2 groups: BIC group: a 10-minute treatment with 10 μ mol/L BIC was performed prior to titanic stimulation; BIC+ Ro25-6981 group: 3 μ mol/L Ro25-6981 and 10 μ mol/L BIC were simultaneously perfused 10 minutes prior to tetanic stimulation.


LTP recording results.


①After 50-60 minutes of titanic stimulation, LTP was (107.85±1.34)% and (100.75±2.75)% in the ACSF and ACSF+ Ro25-6981 groups, respectively, with a significant difference between the two groups (P < 0.05). ② After 50-60 minutes of titanic stimulation, LTP was (164.67±2.40)% and (147.56±6.63)% in the BIC and BIC+ Ro25-6981 groups, respectively, and a significant difference existed between the two groups (P < 0.05).


In the rat hippocampal dentate gyrus, NR2B receptor antagonist Ro25-6981 blocked ACSF-LTP and partly inhibited BIC-LTP, indicating that NR2B receptor antagonist can inhibit newborn neuron-induced LTP.

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