Alteration in RGS2 expression level is associated with changes in haloperidol induced extrapyramidal features in a mutant mouse model

Lior Greenbaum, Tzuri Lifschytz, Polina Zozulinsky, Esther C. Broner, Alexandra Slonimsky, Yoav Kohn, Bernard Lerer

Research output: Contribution to journalArticlepeer-review

Abstract

Antipsychotic induced Parkinsonism (AIP) is a common adverse effect of antipsychotic drug treatment among schizophrenia patients. Two previous studies showed association of the rs4606 SNP in the 3' untranslated region of the regulator of G protein signaling 2 gene (RGS2) with susceptibility to AIP. Since rs4606 reportedly influences expression of RGS2, we applied a translational approach and studied the effect of chronic (24. days) exposure to haloperidol on AIP-like features in mice carrying a mutation that causes lower Rgs2 gene expression. Haloperidol and vehicle treated male mice heterozygous (HET) or homozygous (HOM) for the mutation, or wild type (WT), were evaluated for open field locomotion, catalepsy duration, pole test performance and rota-rod latency to fall. We showed that in haloperidol treated mice lower Rgs2 expression is associated with better performance on the open field, catalepsy and rota-rod tests but not the pole test. Results were most consistent for the 0.2. mg/kg/d haloperidol dose. These observations support the possible involvement of RGS2 in mechanisms underlying susceptibility to AIP.

Original languageEnglish
Pages (from-to)379-386
Number of pages8
JournalEuropean Neuropsychopharmacology
Volume22
Issue number5
DOIs
StatePublished - May 2012
Externally publishedYes

Keywords

  • Antipsychotic induced Parkinsonism
  • Extrapyramidal symptoms
  • Neuroleptics
  • RGS2
  • Schizophrenia

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