Drastic decrease in dopamine receptor levels in the striatum of acetylcholinesterase knock-out mouse

Anna Hrabovska, Vladimir Farar, Veronique Bernard, Ellen G. Duysen, Jiri Brabec, Oksana Lockridge, Jaromir Myslivecek

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Background: The acetylcholinesterase knock-out mouse lives to adulthood despite 60-fold elevated acetylcholine concentrations in the brain that are lethal to wild-type animals. Part of its mechanism of survival is a 50% decrease in muscarinic and nicotinic receptors and a 50% decrease in adrenoceptor levels. Hypothesis: The hypothesis was tested that the dopaminergic neuronal system had also adapted. Methods: Radioligand binding assays measured dopamine receptor level and binding affinity in the striatum. Immunohistochemistry of brain sections with specific antibodies visualized dopamine transporter. Effects on the intracellular compartment were measured as cAMP content, PI-phospholipase C activity. Results: Dopamine receptor levels were decreased 28-fold for the D1-like, and more than 37-fold for the D2-like receptors, though binding affinity was normal. Despite these huge changes in receptor levels, dopamine transporter levels were not affected. The intracellular compartment had normal levels of cAMP and PI-phospholipase C activity. Conclusion: Survival of the acetylcholinesterase knock-out mouse could be linked to adaptation of many neuronal systems during development including the cholinergic, adrenergic and dopaminergic. These adaptations balance the overstimulation of cholinergic receptors caused by high acetylcholine concentrations and thus maintain homeostasis inside the cell, allowing the animal to live.

Original languageEnglish (US)
Pages (from-to)194-201
Number of pages8
JournalChemico-Biological Interactions
Volume183
Issue number1
DOIs
StatePublished - Jan 5 2010

Keywords

  • AChE-/- mouse
  • Adaptation changes
  • Cholinergic system
  • Dopaminergic system
  • Striatum

ASJC Scopus subject areas

  • Toxicology

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