title: Effect of acute NR2B antagonist treatment on long-term potentiation in the rat hippocampus.
abstract: The long lasting antidepressant response seen following acute, i.v. ketamine administration in patients with treatment-resistant depression (TRD) is thought to result from enhanced synaptic plasticity in cortical and hippocampal circuits. Using extracellular field recordings in rat hippocampal slices, we show that a single dose of the non-selective NMDA receptor antagonist ketamine or CP-101,606, a selective antagonist of the NR2B subunit of the NMDA receptor, enhances hippocampal synaptic plasticity induced with high frequency stimulation (HFS) 24h after dosing - a time at which plasma concentrations of the drug are no longer detectable in the animal. These results indicate that acute inhibition of NMDA receptors containing the NR2B subunit can lead to long-lasting changes in hippocampal plasticity.
authors: Neuroscience Biology, Bristol-Myers Squibb Company, Wallingford, CT, USA. Electronic address: john.graef@bms.com.
authors: John D
authors: JD
authors: Graef
authors: Neuroscience Biology, Bristol-Myers Squibb Company, Wallingford, CT, USA.
authors: Kimberly
authors: K
authors: Newberry
authors: Neuroscience Biology, Bristol-Myers Squibb Company, Wallingford, CT, USA.
authors: Amy
authors: A
authors: Newton
authors: Neuroscience Biology, Bristol-Myers Squibb Company, Wallingford, CT, USA.
authors: Rick
authors: R
authors: Pieschl
authors: Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Company, Wallingford, CT, USA.
authors: Eric
authors: E
authors: Shields
authors: Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Company, Wallingford, CT, USA.
authors: Fu-Ni
authors: FN
authors: Luan
authors: Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Company, Wallingford, CT, USA.
authors: Jean
authors: J
authors: Simmermacher
authors: Neuroscience Clinical Biomarkers, Bristol-Myers Squibb Company, Wallingford, CT, USA.
authors: David
authors: D
authors: Luchetti
authors: Neuroscience Clinical Biomarkers, Bristol-Myers Squibb Company, Wallingford, CT, USA.
authors: Eric
authors: E
authors: Schaeffer
authors: Neuroscience Biology, Bristol-Myers Squibb Company, Wallingford, CT, USA.
authors: Yu-Wen
authors: YW
authors: Li
authors: Neuroscience Biology, Bristol-Myers Squibb Company, Wallingford, CT, USA.
authors: Laszlo
authors: L
authors: Kiss
authors: Neuroscience Biology, Bristol-Myers Squibb Company, Wallingford, CT, USA.
authors: Linda J
authors: LJ
authors: Bristow
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000493:pharmacokinetics / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D007649:Ketamine / Q000494:pharmacology*; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D010880:Piperidines / Q000493:pharmacokinetics / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013997:Time Factors; D046509:Tissue Culture Techniques
chemical_list: D000928:Antidepressive Agents; D018691:Excitatory Amino Acid Antagonists; C121001:NR2B NMDA receptor; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine; C095106:traxoprodil mesylate
keywords: Ex vivo; Hippocampus; Long-term potentiation; NMDA receptors; NR2B subunit; Plasticity; Treatment-resistant depression