Effects of haloperidol and clozapine on synapse-related gene expression in specific brain regions of male rats

  • Martina von Wilmsdorff
  • Fabian Manthey
  • Marie-Luise BouvierEmail author
  • Oliver Staehlin
  • Peter Falkai
  • Eva Meisenzahl-Lechner
  • Andrea Schmitt
  • Peter J. Gebicke-Haerter
Original Paper


We investigated the effects of clozapine and haloperidol, drugs that are widely used in the treatment of schizophrenia, on gene expression in six cortical and subcortical brain regions of adult rats. Drug treatments started at postnatal day 85 and continued over a 12-week period. Ten animals received haloperidol (1 mg/kg bodyweight) and ten received clozapine (20 mg/kg bodyweight) orally each day. Ten control rats received no drugs. The ten genes selected for this study did not belong to the dopaminergic or serotoninergic systems, which are typically targeted by the two substances, but coded for proteins of the cytoskeleton and proteins belonging to the synaptic transmitter release machinery. Quantitative real-time PCR was performed in the prelimbic cortex, cingulate gyrus (CG1) and caudate putamen and in the hippocampal cornu ammonis 1 (CA1), cornu ammonis 3 (CA3) and dentate gyrus. Results show distinct patterns of gene expression under the influence of the two drugs, but also distinct gene regulations dependent on the brain regions. Haloperidol-medicated animals showed statistically significant downregulation of SNAP-25 in CA3 (p = 0.0134) and upregulation of STX1A in CA1 (p = 0.0133) compared to controls. Clozapine-treated animals showed significant downregulation of SNAP-25 in CG1 (p = 0.0013). Our results clearly reveal that the drugs’ effects are different between brain regions. These effects are possibly indirectly mediated through feedback mechanisms by proteins targeted by the drugs, but direct effects of haloperidol or clozapine on mechanisms of gene expression cannot be excluded.


Presynaptic proteins Cytoskeletal proteins BDNF Gene expression Schizophrenia 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Supplementary material

406_2018_872_MOESM1_ESM.docx (361 kb)
Supplementary material 1 (DOCX 361 KB)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Martina von Wilmsdorff
    • 1
  • Fabian Manthey
    • 2
  • Marie-Luise Bouvier
    • 3
    Email author
  • Oliver Staehlin
    • 4
  • Peter Falkai
    • 5
  • Eva Meisenzahl-Lechner
    • 1
  • Andrea Schmitt
    • 5
    • 6
  • Peter J. Gebicke-Haerter
    • 7
    • 8
  1. 1.Department of Psychiatry and Psychotherapy, Medical FacultyHeinrich-Heine-UniversityDüsseldorfGermany
  2. 2.Department of Psychiatry and PsychotherapyAlexianer Krefeld GmbHKrefeldGermany
  3. 3.Laboratory of Brain Morphology, Department of Psychiatry and Psychotherapy, LVR KlinikumHeinrich-Heine-UniversityDüsseldorfGermany
  4. 4.Thermo Fisher Sci.DarmstadtGermany
  5. 5.Department of Psychiatry and PsychotherapyLudwig Maximilians-University (LMU) MunichMunichGermany
  6. 6.Laboratory of Neuroscience (LIM27), Institute of PsychiatryUniversity of Sao PauloSão PauloBrazil
  7. 7.Central Institute of Mental HealthMedical Faculty Mannheim/Heidelberg UniversityMannheimGermany
  8. 8.Facultad de MedicinaUniversidad de ChileSantiagoChile

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