title: Chronic haloperidol-induced spatial memory deficits accompany the upregulation of D(1) and D(2) receptors in the caudate putamen of C57BL/6 mouse.
abstract: OBJECTIVE
  Haloperidol (HAL) is an antipsychotic drug that has high affinities to the dopamine D(2), but low affinities to D(1) receptors in the brain. Of brain regions, caudate putamen (CP) has the highest levels of the D(1) and D(2) receptors. In this study we evaluated the spatial memory of C57BL/6 mice following chronic administration of HAL and measured levels of D(1) and D(2) receptors in specific brain regions, with the hypothesis that the D(1) and D(2) receptors in CP are important players in spatial memory function of the brain.
  
  
  METHODS
  C57BL/6 mice received daily intraperitoneal injections of saline or HAL at 1.0 or 2.0mg/kg/day for 3 or 6 weeks. Two days after the last injection, spontaneous alternation of mice in a Y-maze was evaluated to measure their exploratory behavior and spatial working memory. The Morris water maze test was performed to measure their spatial learning and memory. D(1) and D(2) receptors in specific brain regions were measured by Western-blot analysis.
  
  
  RESULTS
  HAL treatment for 6 weeks decreased the spontaneous alternation of mice in Y-maze, altered the acquisition process and impaired spatial memory in Morris water maze. The same treatment increased levels of D(1) and D(2) receptors in CP and up-regulated D(2) receptors in the hippocampus, but did not change the receptors in the prefrontal cortex.
  
  
  CONCLUSIONS
  These results suggest that the D(1) and D(2) receptors in CP are among the main targets of HAL and the receptors in CP play an important role in spatial learning and memory.
authors.affiliation: Department of Anatomy, Southern Illinois University Carbondale, Carbondale, IL, USA. hyxu@stu.edu.cn
authors.forename: Haiyun
authors.initials: H
authors.lastname: Xu
authors.forename: Hong-Ju
authors.initials: HJ
authors.lastname: Yang
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Rose
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000633:toxicity*; D001522:Behavior, Animal / Q000187:drug effects; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006220:Haloperidol / Q000008:administration & dosage / Q000633:toxicity*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D008569:Memory Disorders / Q000139:chemically induced*; D051379:Mice; D008810:Mice, Inbred C57BL; D011699:Putamen / Q000187:drug effects / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000235:genetics / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D014150:Antipsychotic Agents; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D006220:Haloperidol