title: Enhanced dopamine-dependent hippocampal plasticity after single MK-801 application.
abstract: Dopaminergic hyperfunction and N-methyl-D-aspartate receptor (NMDAR) hypofunction have both been implicated in psychosis. Dopamine-releasing drugs and NMDAR antagonists replicate symptoms associated with psychosis in healthy humans and exacerbate symptoms in patients with schizophrenia. Though hippocampal dysfunction contributes to psychosis, the impact of NMDAR hypofunction on hippocampal plasticity remains poorly understood. Here, we used an NMDAR antagonist rodent model of psychosis to investigate hippocampal long-term potentiation (LTP). We found that single systemic NMDAR antagonism results in a region-specific, presynaptic LTP at hippocampal CA1-subiculum synapses that is induced by activation of D1/D5 dopamine receptors and modulated by L-type voltage-gated Ca(2+) channels. Thereby, our findings may provide a cellular mechanism how NMDAR antagonism can lead to an enhanced hippocampal output causing activation of the hippocampus-ventral tegmental area-loop and overdrive of the dopamine system.
authors.affiliation: 1] Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Berlin, Germany [2] Institute of Neurophysiology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Julia C
authors.initials: JC
authors.lastname: Bartsch
authors.affiliation: 1] Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Berlin, Germany [2] Institute of Neurophysiology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Pawel
authors.initials: P
authors.lastname: Fidzinski
authors.affiliation: Department of Neuropsychiatry and Laboratory of Molecular Psychiatry, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Jojanneke H J
authors.initials: JH
authors.lastname: Huck
authors.affiliation: Institute of Pharmacology and Toxicology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Heide
authors.initials: H
authors.lastname: Hörtnagl
authors.affiliation: Institute of Neurophysiology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Richard
authors.initials: R
authors.lastname: Kovács
authors.affiliation: Institute of Neurophysiology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Agustin
authors.initials: A
authors.lastname: Liotta
authors.affiliation: 1] Department of Neuropsychiatry and Laboratory of Molecular Psychiatry, Charité - Universitätsmedizin Berlin, Berlin, Germany [2] Cluster of Excellence NeuroCure, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Josef
authors.initials: J
authors.lastname: Priller
authors.affiliation: Neuroscience Research Center, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Wozny
authors.affiliation: 1] Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Berlin, Germany [2] Institute of Neurophysiology, Charité - Universitätsmedizin Berlin, Berlin, Germany [3] Department of Psychiatry and Psychotherapy, Ruppiner Kliniken, Neuruppin, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Behr
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D058787:GABA-A Receptor Antagonists; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D000262:Adenylyl Cyclases; D009543:Nifedipine; D002118:Calcium; D004298:Dopamine; D001640:Bicuculline