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

Bartsch, Julia C and Fidzinski, Pawel and Huck, Jojanneke HJ and Hörtnagl, Heide and Kovács, Richard and Liotta, Agustin and Priller, Josef and Wozny, Christian and Behr, Joachim (2015) Enhanced dopamine-dependent hippocampal plasticity after single MK-801 application. Neuropsychopharmacology, 40 (4). pp. 987-995. ISSN 1470-634X

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    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.