Enhanced dopamine-dependent hippocampal plasticity after single MK-801 application

Julia C Bartsch, Pawel Fidzinski, Jojanneke H J Huck, Heide Hörtnagl, Richard Kovács, Agustin Liotta, Josef Priller, Christian Wozny, Joachim Behr

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)987-95
Number of pages9
JournalNeuropsychopharmacology
Volume40
Issue number4
Early online date15 Oct 2014
DOIs
Publication statusE-pub ahead of print - 15 Oct 2014

Keywords

  • Adenylyl Cyclases
  • Animals
  • Bicuculline
  • Calcium
  • Calcium Channel Blockers
  • Dizocilpine Maleate
  • Dopamine
  • Enzyme Inhibitors
  • Excitatory Amino Acid Antagonists
  • GABA-A Receptor Antagonists
  • Glutamic Acid
  • Hippocampus
  • In Vitro Techniques
  • Long-Term Potentiation
  • Male
  • Nifedipine
  • Rats
  • Rats, Wistar
  • Signal Transduction
  • Journal Article
  • Research Support, Non-U.S. Gov't

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