OSCR

A single dose of the antipsychotic drug clozapine has long-term behavioral and functional effects in mice

Overview

Authors: Leonardo Lupori1, Matthias Heindorf1, Stylianos Kouvaros2, Alice Schildkamp1, Josef Bischofberger2, Georg B. Keller1,2
ORCID iDs: Leonardo Lupori, Matthias Heindorf, Stylianos Kouvaros, Josef Bischofberger, Georg B. Keller
  1. Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland
  2. Faculty of Science, Department of Biomedicine, University of Basel, Basel, Switzerland
Institutions: Friedrich Miescher Institute (Switzerland); University of Basel (Switzerland)
Journal: bioRxiv (preprint)
Dates: published online 31 March 2026
Type: Preprint
License: CC BY-NC
Identifiers: DOI 10.64898/2026.03.27.714783 · OpenAlex W7147475033
Open access: green, a free copy (OpenAlex)
Status: code verified (how the code is found and verified)
Categories: mouse (organism), schizophrenia / psychosis (population)
Methods: Spectral & time-frequency, Connectivity, Statistics, Smoothing, state filtering, decompositions, Machine learning, Preprocessing, fMRI & imaging, Single-unit activity, calcium imaging
Topic: Schizophrenia research and treatment (Psychiatry and Mental health, Medicine), according to OpenAlex
Citations: cited by 3 papers (Europe PMC); 99 references in the paper

Abstract

Antipsychotic dosing regimens, commonly daily or via slow-release compounds, are designed to maintain steady-state plasma concentrations. They are guided by their plasma half-life that is typically in the range of several hours. This schedule contrasts with the slow time course of therapeutic efficacy, which often takes weeks to develop fully. This discrepancy led us to hypothesize that the effects of a single dose of an antipsychotic drug might be detectable well beyond the time window predicted by receptor occupancy. To test this, we administered a single dose of the antipsychotic drug clozapine to mice. We observed long-term behavioral effects and changes to cortical activity patterns up to several days after administration. Specifically, clozapine induced a decorrelation of activity in the dorsal cortex observable up to 9 days post administration. This effect was driven by a genetically and functionally distinct subset of layer 5 intratelencephalic neurons, possibly through a clozapine induced increase in the reliability of long-range inhibitory functional influence that exhibited a similar long-term change. Thus, our findings suggest that longer dosing intervals for antipsychotic drugs warrant clinical exploration.

Reproduced under the paper's license (CC BY-NC), from the paper cited above.

Code

No file of the authors' code could be read here: it is described below, and read at its source.

sourceforge.net/iris-scanning

License: none: the authors keep all their rights
State: the link answers, verified on 3 November 2026
Evidence: the link answers
Software Heritage: not checked
Found in: “Data Availability”
Not found: README, license file, CITATION.cff, environment file, tests, continuous integration, documentation
Availability: 2 checks, the latest on 3 November 2026: the link answers (HTTP 200)
  • 3 November 2026: the link answers (HTTP 200)
  • 30 September 2026: the link answers (HTTP 200)
At the source: sourceforge.net/projects/iris-scanning/

The paper's code and data availability statement is in the Data section.

Tracing map

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  • 0 scripts, each with its path and the digest of its content;
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Data

No dataset and no data link were found in the paper.

Data Availability

Software for controlling the two-photon and widefield microscopes and preprocessing of calcium imaging data is available on https://sourceforge.net/projects/iris-scanning/. Raw data and code to generate all figures will be deposited in public repositories upon publication.

Reproduced under the paper's license (CC BY-NC), from the paper cited above.

Versions

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Version 1, 30 September 2026: the first record

Recorded: type, journal, dates, 6 authors, 96 references.

Cite

This paper

Lupori, L., Heindorf, M., Kouvaros, S., Schildkamp, A., Bischofberger, J., & Keller, G. B. (2026). A single dose of the antipsychotic drug clozapine has long-term behavioral and functional effects in mice. bioRxiv (preprint). https://doi.org/10.64898/2026.03.27.714783

BibTeX

@article{lupori2026single,
author = {Lupori, Leonardo and Heindorf, Matthias and Kouvaros, Stylianos and Schildkamp, Alice and Bischofberger, Josef and Keller, Georg B.},
title = {{A single dose of the antipsychotic drug clozapine has long-term behavioral and functional effects in mice}},
journal = {bioRxiv (preprint)},
year = {2026},
month = mar,
publisher = {bioRxiv},
issn = {2692-8205},
doi = {10.64898/2026.03.27.714783},
url = {https://doi.org/10.64898/2026.03.27.714783}
}

RIS

TY - JOUR
AU - Lupori, Leonardo
AU - Heindorf, Matthias
AU - Kouvaros, Stylianos
AU - Schildkamp, Alice
AU - Bischofberger, Josef
AU - Keller, Georg B.
TI - A single dose of the antipsychotic drug clozapine has long-term behavioral and functional effects in mice
T2 - bioRxiv (preprint)
J2 - bioRxiv
PY - 2026
DA - 2026/03/31
SN - 2692-8205
PB - bioRxiv
DO - 10.64898/2026.03.27.714783
UR - https://doi.org/10.64898/2026.03.27.714783
ER -

CSL-JSON

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