title: The Effects of Different Concentrations of the α2-Adrenoceptor Agonist Medetomidine on Basal Excitatory Synaptic Transmission and Synaptic Plasticity in Hippocampal Slices of Adult Mice.
abstract: BACKGROUND
  α2-Adrenoceptor agonists are used frequently in human and veterinary anesthesia as sedative/analgesic drugs. However, they can impair cognition. Little is known about the concentration-dependent effects of α2-adrenoceptor agonists on synaptic plasticity, the neurophysiological basis of learning and memory. Therefore, we investigated the effects of different concentrations of medetomidine, an α2-adrenoceptor agonist, on basal excitatory synaptic transmission and on 2 forms of synaptic plasticity: paired-pulse facilitation (PPF) and long-term potentiation (LTP).
  
  
  METHODS
  Evoked field excitatory postsynaptic potentials were recorded in Schaffer fibers-CA1 pyramidal cell synapses of mouse hippocampal slices, and the initial field excitatory postsynaptic potentials slope was measured. For basal synaptic transmission and PPF, increasing concentrations of medetomidine (1-200 μM) were applied to each slice. For LTP experiments, individual slices were used for each tested concentration of medetomidine (0.1-0.4 μM), where LTP induction and LTP maintenance were measured.
  
  
  RESULTS
  The lower tested concentrations of medetomidine decreased LTP in a concentration-dependent manner, whereas greater concentrations were required to decrease fiber volley amplitude and basal excitatory synaptic transmission. PPF was only affected by the greatest concentration (200 μM).
  
  
  CONCLUSIONS
  Medetomidine decreased LTP in the mouse hippocampus, in accordance with the ability of medetomidine to induce memory deficits.
authors: From the Center for Neuroscience and Cell Biology (CNC), University of Coimbra, Coimbra, Portugal; Department of Veterinary Sciences, Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAD), University of Trás-os-Montes and Alto Douro (UTAD), Quinta de Prados, Vila Real, Portugal; Institute of Molecular and Cell Biology (IBMC), Porto, Portugal; Department of Sciences and Technology, Portuguese Open University, Delegação do Porto, Porto, Portugal; Anaesthesiology Service, Clinical Anaesthesiology Research Centre, Centro Hospitalar do Porto, Porto, Portugal; Faculty of Medicine, University of Coimbra, Coimbra, Portugal; and Department of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, Coimbra, Portugal.
authors: Patrícia O
authors: PO
authors: Ribeiro
authors: Luis M
authors: LM
authors: Antunes
authors: Catarina S
authors: CS
authors: Nunes
authors: Henrique B
authors: HB
authors: Silva
authors: Rodrigo A
authors: RA
authors: Cunha
authors: Ângelo R
authors: ÂR
authors: Tomé
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology* / Q000633:toxicity; D000367:Age Factors; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005071:Evoked Potentials / Q000187:drug effects; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects*; D005260:Female; D066298:In Vitro Techniques; D036881:Long-Term Synaptic Depression / Q000187:drug effects; D020926:Medetomidine / Q000494:pharmacology* / Q000633:toxicity; D008568:Memory / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D009473:Neuronal Plasticity / Q000187:drug effects*; D017966:Pyramidal Cells / Q000187:drug effects* / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects*; D013997:Time Factors
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D020926:Medetomidine