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Dexmedetomidine Reduces Long-term Potentiation in Mouse Hippocampus

Background:Dexmedetomidine (Precedex; Abbott Laboratories, Abbott Park, IL) is a selective &agr;2-adrenergic agonist that also has affinity for imidazoline receptors. In clinical studies, dexmedetomidine has sedative effects and impairs memory, but the action of dexmedetomidine on synaptic plasticity in the brain has yet to be established. In the present study, the authors investigated the effects of dexmedetomidine on two forms of synaptic plasticity—long-term potentiation (LTP) and paired-pulse facilitation—in the CA1 region of mouse hippocampal slices. Methods:The authors recorded Schaffer collateral-evoked field excitatory postsynaptic potentials from mouse hippocampal slices in CA1 stratum radiatum. The slope of the rising phase of the field excitatory postsynaptic potential was used to estimate the strength of synaptic transmission. Results:Application of dexmedetomidine for 20 min before “theta burst” stimulation dose-dependently attenuated LTP, and half-inhibitory concentration of dexmedetomidine was 28.6 ± 5.7 nm. The inhibitory effect of dexmedetomidine on LTP was not abolished by an &agr;2-adrenoceptor antagonist (yohimbine), an imidazoline type 1 receptor and &agr;2-adrenoceptor antagonist (efaroxan), an &agr;1-adrenoceptor antagonist (prazosin), or a &ggr;-aminobutyric acid type A receptor antagonist (picrotoxin). However, an imidazoline type 2 receptor and &agr;2-adrenoceptor antagonist (idazoxan) completely blocked the dexmedetomidine-induced attenuation. Furthermore, 2-benzofuranyl-2-imidaloline, a selective imidazoline type 2 receptor ligand, reduced LTP. 2-(4,5-dihydroimidaz-2-yl)-quinoline, another imidazoline type 2 receptor ligand, abolished the 2-benzofuranyl-2-imidaloline-induced attenuation, but the inhibitory effect of dexmedetomidine on LTP was not abolished by 2-(4,5-dihydroimidaz-2-yl)-quinoline. Dexmedetomidine did not affect paired-pulse facilitation. Conclusion:Dexmedetomidine impairs LTP in area CA1 of the mouse hippocampus via imidazoline type 2 receptors and &agr;2-adrenoceptors.