title: NMDA receptor antagonists ketamine and Ro25-6981 inhibit evoked release of glutamate in vivo in the subiculum.
abstract: Preclinical and clinical data have identified ketamine, a non-selective NMDAR (N-methyl-D-aspartate receptor) antagonist, as a promising medication for patients who do not respond to treatment with monoamine-based antidepressants. Moreover, unlike the current monoamine-based antidepressants, ketamine has a long-lasting effect already after a single dose. The mechanisms of ketamine action remain to be fully understood. Using a recently developed microelectrode array (MEA), which allows sub-second measurements of fluctuating glutamate concentrations, we studied here the effects of in vivo local application of the ketamine and of the N2B subunit-specific antagonist Ro25-6981 upon evoked glutamate release. Both ligands inhibit glutamate release in subregions of the hippocampus and prefrontal cortex. Likewise, acute systemic ketamine treatment, at an antidepressant dose, caused a reduction in evoked glutamate release in the subiculum. We suggest that the effects of ketamine and Ro25-6981 in the subiculum could involve blockade of presynaptic NMDA receptors containing N2B subunits.
authors.affiliation: Section of Translational Neuropharmacology, Department of Clinical Neuroscience, Laboratory of Translational Neuropharmacology, Center of Molecular Medicine, Karolinska Institute, Stockholm, Sweden.
authors.forename: T L
authors.initials: TL
authors.lastname: Stan
authors.affiliation: Section of Translational Neuropharmacology, Department of Clinical Neuroscience, Laboratory of Translational Neuropharmacology, Center of Molecular Medicine, Karolinska Institute, Stockholm, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Alvarsson
authors.affiliation: Section of Translational Neuropharmacology, Department of Clinical Neuroscience, Laboratory of Translational Neuropharmacology, Center of Molecular Medicine, Karolinska Institute, Stockholm, Sweden.
authors.forename: N
authors.initials: N
authors.lastname: Branzell
authors.affiliation: Section of Translational Neuropharmacology, Department of Clinical Neuroscience, Laboratory of Translational Neuropharmacology, Center of Molecular Medicine, Karolinska Institute, Stockholm, Sweden.
authors.forename: V C
authors.initials: VC
authors.lastname: Sousa
authors.affiliation: Section of Translational Neuropharmacology, Department of Clinical Neuroscience, Laboratory of Translational Neuropharmacology, Center of Molecular Medicine, Karolinska Institute, Stockholm, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Svenningsson
mesh_terms: D000818:Animals; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D018698:Glutamic Acid / Q000187:drug effects / Q000600:supply & distribution*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007649:Ketamine / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008839:Microelectrodes; D010636:Phenols / Q000008:administration & dosage / Q000494:pharmacology; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D011897:Random Allocation; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
chemical_list: D018691:Excitatory Amino Acid Antagonists; C121001:NR2B NMDA receptor; D010636:Phenols; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; C109643:Ro 25-6981; D018698:Glutamic Acid; D007649:Ketamine