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

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Abstract

BACKGROUND:

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.

OBJECTIVE:

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

DESIGN, TIME AND SETTING:

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

MATERIALS:

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

METHODS:

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.

MAIN OUTCOME MEASURES:

LTP recording results.

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).

CONCLUSION:

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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