A dopaminergic mechanism of antipsychotic drug efficacy, failure, and failure reversal: the role of the dopamine transporter

Beitrag in einer Fachzeitschrift


Details zur Publikation

Autorinnen und Autoren: Amato D, Canneva F, Cumming P, Maschauer S, Groos D, Dahlmanns JK, Grömer TW, Chiofalo L, Dahlmanns M, Zheng F, Kornhuber J, Prante O, Alzheimer C, von Hörsten S, Müller CP
Zeitschrift: Molecular Psychiatry
Jahr der Veröffentlichung: 2018
ISSN: 1359-4184


Abstract

Antipsychotic drugs are effective interventions in schizophrenia. However, the efficacy of these agents often decreases over time, which leads to treatment failure and symptom recurrence. We report that antipsychotic efficacy in rat models declines in concert with extracellular striatal dopamine levels rather than insufficient dopamine D2 receptor occupancy. Antipsychotic efficacy was associated with a suppression of dopamine transporter activity, which was reversed during failure. Antipsychotic failure coincided with reduced dopamine neuron firing, which was not observed during antipsychotic efficacy. Synaptic field responses in dopamine target areas declined during antipsychotic efficacy and showed potentiation during failure. Antipsychotics blocked synaptic vesicle release during efficacy but enhanced this release during failure. We found that the pharmacological inhibition of the dopamine transporter rescued antipsychotic drug treatment outcomes, supporting the hypothesis that the dopamine transporter is a main target of antipsychotic drugs and predicting that dopamine transporter blockers may be an adjunct treatment to reverse antipsychotic treatment failure.


FAU-Autorinnen und Autoren / FAU-Herausgeberinnen und Herausgeber

Alzheimer, Christian Prof. Dr.
Lehrstuhl für Physiologie
Amato, Davide PD Dr.
Psychiatrische und Psychotherapeutische Klinik
Chiofalo, Lisa
Medizinische Fakultät
Dahlmanns, Marc
Lehrstuhl für Physiologie
Groos, Dominik
Lehrstuhl für Physiologie
Kornhuber, Johannes Prof. Dr. med.
Lehrstuhl für Psychiatrie und Psychotherapie
Maschauer, Simone PD Dr.
Nuklearmedizinische Klinik
Müller, Christian P. Prof. Dr.
Professur für Suchtmedizin
Prante, Olaf Prof. Dr.
Professur für Molekulare Bildgebung und Radiochemie
von Hörsten, Stephan Prof. Dr.
Professur für Experimentelle Biomedizin
Zheng, Fang
Lehrstuhl für Physiologie


Einrichtungen weiterer Autorinnen und Autoren

Medical University of South Carolina (MUSC)


Zitierweisen

APA:
Amato, D., Canneva, F., Cumming, P., Maschauer, S., Groos, D., Dahlmanns, J.K.,... Müller, C.P. (2018). A dopaminergic mechanism of antipsychotic drug efficacy, failure, and failure reversal: the role of the dopamine transporter. Molecular Psychiatry. https://dx.doi.org/10.1038/s41380-018-0114-5

MLA:
Amato, Davide, et al. "A dopaminergic mechanism of antipsychotic drug efficacy, failure, and failure reversal: the role of the dopamine transporter." Molecular Psychiatry (2018).

BibTeX: 

Zuletzt aktualisiert 2019-08-03 um 12:38