Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Sensitization with clozapine: beyond the dopamine hypothesis

J R Stevens1, D Denney, P Szot

  • 1Department of Neurology and Psychiatry, Oregon Health Sciences University, Portland 97201, USA.

Biological Psychiatry
|November 5, 1997
PubMed
Summary

Repeated low doses of clozapine can induce myoclonic jerks in rats through sensitization. This sensitization alters gene expression, potentially linking central excitatory effects to clozapine's therapeutic action in psychosis.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Search for the Y(2175) in the Photoproduction Cross Section Measurement of γp→ϕπ^{+}π^{-}p at GlueX.

Physical review letters·2026
Same author

Upper Limit on the Photoproduction Cross Section of the Spin-Exotic π_{1}(1600).

Physical review letters·2025
Same author

Ocean-wide genomic variation in Gray's beaked whales, <i>Mesoplodon grayi</i>.

Royal Society open science·2021
Same author

Ecological and geographical speciation in <i>Lucilia</i> <i>bufonivora</i>: The evolution of amphibian obligate parasitism.

International journal for parasitology. Parasites and wildlife·2019
Same author

First Measurement of Near-Threshold J/ψ Exclusive Photoproduction off the Proton.

Physical review letters·2019
Same author

Spatial and temporal habitat partitioning by calliphorid blowflies.

Medical and veterinary entomology·2018

Area of Science:

  • Neuropharmacology
  • Psychiatry
  • Molecular Neuroscience

Background:

  • Clozapine is known to cause dose-dependent myoclonic jerks and seizures in patients.
  • The central excitatory effects of clozapine are hypothesized to be linked to its therapeutic efficacy.
  • Sensitization and kindling are mechanisms by which repeated drug administration can lead to enhanced central effects.

Purpose of the Study:

  • To investigate if repeated, very low-dose clozapine administration can induce central excitatory effects via sensitization or kindling in rats.
  • To explore the relationship between clozapine-induced central excitation and its potential therapeutic mechanisms.

Main Methods:

  • Rats received repeated, very low-dose (1 mg/kg) clozapine injections on alternate-day or weekly schedules.

Related Experiment Videos

  • Behavioral monitoring for myoclonic seizure-like jerks (MJs) was conducted.
  • Early gene expression patterns in subcortical sites were compared between clozapine-sensitized and vehicle-treated control rats.

    • Main Results:

    • Repeated low-dose clozapine administration, despite initial lack of effect, led to a significant increase in MJs over successive injections.
    • Animals treated with repeated low-dose clozapine exhibited 75-110 MJs/hour by the sixth injection.
    • Clozapine-sensitized animals showed distinct early gene expression profiles in specific subcortical regions compared to controls.

    Conclusions:

    • Repeated administration of very low-dose clozapine can induce a sensitization phenomenon, leading to myoclonic seizure-like activity.
    • The observed changes in gene expression suggest a neurobiological basis for clozapine-induced central excitation.
    • These findings may offer insights into the mechanisms underlying clozapine's effectiveness in treating psychosis.