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Related Experiment Videos

Mapping the genes for haloperidol-induced catalepsy

S Kanes1, K Dains, L Cipp

  • 1Department of Psychiatry, State University of New York at Stony Brook, USA.

The Journal of Pharmacology and Experimental Therapeutics
|May 1, 1996
PubMed
Summary

Genetic analysis in mice reveals quantitative trait loci (QTLs) influencing haloperidol-induced catalepsy and D2 dopamine receptor binding. A key QTL on chromosome 9 is linked to the Drd2 gene, impacting both traits.

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Area of Science:

  • Neurogenetics
  • Pharmacogenetics
  • Behavioral Neuroscience

Background:

  • Haloperidol is a typical antipsychotic drug used to treat psychosis.
  • Catalepsy is a motor symptom that can be induced by haloperidol and is used as a model for antipsychotic drug response.
  • Genetic factors significantly influence individual responses to psychotropic medications.

Purpose of the Study:

  • To identify quantitative trait loci (QTLs) associated with haloperidol-induced catalepsy in mice.
  • To investigate the genetic relationship between haloperidol response and D2 dopamine receptor binding.
  • To determine if the D2 dopamine receptor gene (Drd2) is a QTL influencing these phenotypes.

Main Methods:

  • Utilized the BXD recombinant inbred series of mice to map QTLs for haloperidol-induced catalepsy.

Related Experiment Videos

  • Correlated strain means with genetic markers to identify QTLs.
  • Confirmed QTLs in an F2 intercross generation (B6XD2).
  • Assessed D2 dopamine receptor binding using [125I] epidepride in F2 mice.

    • Main Results:

    • Identified six QTLs for haloperidol-induced catalepsy (P < .01).
    • Confirmed two QTLs, one on chromosome 4 and another on chromosome 9.
    • The chromosome 9 QTL is closely linked to the Drd2 gene.
    • Individuals with the DBA/2J allele at the chromosome 9 QTL showed higher D2 receptor binding in most brain regions.
    • Drd2 is implicated as a QTL affecting both haloperidol response and D2 receptor binding, but does not account for all genetic variance.

    Conclusions:

    • The Drd2 gene region contains a QTL that significantly influences both haloperidol-induced catalepsy and D2 dopamine receptor binding.
    • While Drd2 plays a role, other genetic factors contribute substantially to the observed variance in these traits.
    • This study provides valuable insights into the genetic architecture of antipsychotic drug response.