title: Clinically relevant concentrations of ketamine mainly affect long-term potentiation rather than basal excitatory synaptic transmission and do not change paired-pulse facilitation in mouse hippocampal slices.
abstract: Ketamine, an analgesic/anesthetic drug, is increasingly popular in clinical practice due to its analgesic properties and importance for emergency procedures. The impact of ketamine on basal excitatory synaptic transmission and synaptic plasticity are not yet fully understood. Therefore we investigated the effects of different concentrations of ketamine on basal excitatory synaptic transmission and on two forms of synaptic plasticity: paired-pulse facilitation (PPF) and long-term potentiation (LTP). Evoked field excitatory postsynaptic potentials (fEPSP) were recorded in Schaffer fiber - CA1 pyramid synapses of mouse hippocampal slices and the initial slope of the fEPSP was measured to estimate the percentage of inhibition of the basal synaptic transmission. Presynaptic volley amplitude, PPF and LTP induction and maintenance were also calculated. For basal synaptic transmission and PPF increasing concentrations of ketamine (1, 3, 10, 30, 100, 200, 300 and 600μM) were applied to each slice and for LTP individual slices were used for each concentration (3, 10, 30 or 100μM). Clinically relevant concentrations of ketamine decreased LTP in a concentration-dependent manner without changing PPF, whereas basal excitatory synaptic transmission and presynaptic volley amplitude was affected only with high concentrations of ketamine (300 and 600μM). These results allow dissociating the blockade of LTP from a reduced synaptic input in the action of clinically relevant concentrations of ketamine in the CA1 region of the mouse hippocampus. Moreover, this work shows that the effects of ketamine on LTP and on basal synaptic transmission are dependent of the concentration used.
authors.affiliation: Instituto de Biologia Molecular e Celular, Laboratory Animal Science, Rua do Campo Alegre 823, 4150-180 Porto, Portugal; Departamento de Ciências Veterinárias, Universidade de Trás-os-Montes e Alto Douro, Apartado 1013, 5001-801 Vila Real, Portugal; CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal. Electronic address: topatricia.ribeiro.fafe@gmail.com.
authors.forename: Patrícia O
authors.initials: PO
authors.lastname: Ribeiro
authors.affiliation: CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal; Departamento das Ciências da Vida, Faculdade de Ciências e Tecnologia, Universidade de Coimbra, 3001-401 Coimbra, Portugal.
authors.forename: Angelo R
authors.initials: AR
authors.lastname: Tomé
authors.affiliation: CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal.
authors.forename: Henrique B
authors.initials: HB
authors.lastname: Silva
authors.affiliation: CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal; Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal.
authors.forename: Rodrigo A
authors.initials: RA
authors.lastname: Cunha
authors.affiliation: Instituto de Biologia Molecular e Celular, Laboratory Animal Science, Rua do Campo Alegre 823, 4150-180 Porto, Portugal; Departamento de Ciências Veterinárias, Universidade de Trás-os-Montes e Alto Douro, Apartado 1013, 5001-801 Vila Real, Portugal.
authors.forename: Luís M
authors.initials: LM
authors.lastname: Antunes
mesh_terms: D000344:Afferent Pathways / Q000187:drug effects / Q000502:physiology; D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000502:physiology; D056654:CA3 Region, Hippocampal / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D007649:Ketamine / Q000494:pharmacology*; D017774:Long-Term Potentiation / Q000187:drug effects*; D008807:Mice, Inbred BALB C; D008839:Microelectrodes; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects*; D046509:Tissue Culture Techniques
chemical_list: D000777:Anesthetics; D007649:Ketamine
keywords: Hippocampus; Ketamine; Synaptic plasticity; Synaptic transmission