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Clonidine Suppresses the Induction of Long-Term Potentiation by Inhibiting HCN Channels at the Schaffer Collateral–CA1 Synapse in Anesthetized Adult Rats

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Abstract

Activation of alpha2-adrenoceptors inhibits long-term potentiation and long-term depression in many brain regions. However, effectiveness and mechanism of alpha2-adrenoceptors for synaptic plasticity at the Schaffer collateral–CA1 synapses in rat in vivo is unclear. In the present study, we investigated the effects of alpha2-adrenoceptors agonist clonidine on high-frequency stimulation (HFS)-induced long-term potentiation (LTP) and paired-pulse facilitation (PPF) at the Schaffer collateral–CA1 synapse of rat hippocampus in vivo. Clonidine (0.05, 0.1 mg/kg, ip) inhibited synaptic plasticity in a dose-dependent manner, accompanying with the decreasing of aortic pressure and heart rate (HR) in anesthetized rats. Clonidine (1.25, 2.5 μg/kg, icv, 10 min before HFS) also dose-dependently inhibited synaptic plasticity, which had no remarkable effect on HR and aortic pressure. But, 20 min after HFS, administration of clonidine (2.5 μg/kg) had no effect on LTP. The inhibitory effect of clonidine (2.5 μg/kg) on LTP was completely reversed by yohimbine (18 μg/kg, icv) and ZD7288 (5 μg/kg, icv). Moreover, the inhibition was accompanied by a significant increase of the normalized PPF ratio. Furthermore, clonidine at 1 and 10 μM significantly decreased glutamate (Glu) content in the culture supernatants of hippocampal neurons, and yohimbine at 1 and 10 μM had no effect on Glu release, while it could reverse the inhibition of clonidine (1 and 10 μM) on Glu release. In conclusion, clonidine can suppress the induction of LTP at the Schaffer collateral–CA1 synapse, and the possible mechanism is that activation of presynaptic alpha2-adrenoceptors reduces the Glu release by inhibiting HCN channels.

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (NSFC, No. 81173038) to Lianjun Guo.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Pharmacology, School of Basic Medical Sciences, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China

    Chang-jun Li, Mei Zhou, Qing Lv, Xu-lin Xu & Lian-jun Guo

  2. Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation, Wuhan, 430030, Hubei, People’s Republic of China

    Chang-jun Li, Qing Lv, Xu-lin Xu & Lian-jun Guo

  3. Department of Pharmacology, Johannes Gutenberg University, Mainz, Germany

    Hui-ge Li

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  1. Chang-jun Li
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  2. Mei Zhou
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  5. Xu-lin Xu
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Correspondence to Lian-jun Guo.

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Li, Cj., Zhou, M., Li, Hg. et al. Clonidine Suppresses the Induction of Long-Term Potentiation by Inhibiting HCN Channels at the Schaffer Collateral–CA1 Synapse in Anesthetized Adult Rats. Cell Mol Neurobiol 33, 1075–1086 (2013). https://doi.org/10.1007/s10571-013-9974-z

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  • DOI: https://doi.org/10.1007/s10571-013-9974-z

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