Selective dopamine D3 receptor antagonists enhance cortical acetylcholine levels measured with high-performance liquid chromatography/tandem mass spectrometry without anti-cholinesterases

J Neurosci Methods. 2006 Oct 15;157(1):25-31. doi: 10.1016/j.jneumeth.2006.03.017. Epub 2006 May 11.


The present study compared the effects of two selective dopamine (DA) D(3) receptor antagonists, SB-277011A (3, 10 and 30 mg/kg i.p.) and SB-414796A (3, 10 and 30 mg/kg i.p.) on extracellular levels of acetylcholine (ACh) in the rat medial prefrontal cortex (mPFC) by using a LC/MS-MS analytical method that permitted the detection of ACh without the necessity of adding acetylcholinesterase inhibitors to the perfusate. Furthermore, the present LC/MS-MS method permitted the simultaneous measurement of the respective concentrations of SB-277011A and SB-414796A in the same extracellular samples from the mPFC. The systemic administration of both selective DA D(3) receptor antagonists produced a significant increase in extracellular levels of Ach compared to vehicle-treated animals, which was associated with increases in extracellular concentrations of SB-277011A and SB-414796. Overall, the present findings further strengthen the likelihood of a modulation of cortical cholinergic function through a DA D(3)-mediated mechanism and suggest that selective DA D(3) receptor antagonism may be beneficial in the treatment of psychiatric diseases, such as schizophrenia, which are characterized by cognitive dysfunction.

Publication types

  • Comparative Study

MeSH terms

  • Acetylcholine / metabolism*
  • Animals
  • Anticholesteremic Agents / pharmacology*
  • Brain Chemistry / drug effects
  • Chromatography, High Pressure Liquid / methods*
  • Dopamine Antagonists / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Extracellular Space / drug effects
  • Heterocyclic Compounds, 2-Ring / pharmacology
  • Male
  • Mass Spectrometry / methods*
  • Microdialysis / methods
  • Oxadiazoles / pharmacology
  • Prefrontal Cortex / drug effects*
  • Rats
  • Rats, Sprague-Dawley


  • Anticholesteremic Agents
  • Dopamine Antagonists
  • Heterocyclic Compounds, 2-Ring
  • Oxadiazoles
  • SB-414796A
  • Acetylcholine