title: Alteration in RGS2 expression level is associated with changes in haloperidol induced extrapyramidal features in a mutant mouse model.
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.
authors: Biological Psychiatry Laboratory, Department of Psychiatry, Hadassah – Hebrew University Medical Center, Jerusalem, Israel.
authors: Lior
authors: L
authors: Greenbaum
authors: Tzuri
authors: T
authors: Lifschytz
authors: Polina
authors: P
authors: Zozulinsky
authors: Esther C
authors: EC
authors: Broner
authors: Alexandra
authors: A
authors: Slonimsky
authors: Yoav
authors: Y
authors: Kohn
authors: Bernard
authors: B
authors: Lerer
mesh_terms: D000818:Animals; D001480:Basal Ganglia Diseases / Q000139:chemically induced* / Q000378:metabolism* / Q000523:psychology; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006220:Haloperidol / Q000494:pharmacology / Q000633:toxicity*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020710:RGS Proteins / Q000096:biosynthesis*
chemical_list: D020710:RGS Proteins; C087182:RGS2 protein, human; D006220:Haloperidol