The muscarinic agonist xanomeline increases monoamine release and immediate early gene expression in the rat prefrontal cortex

Biological Psychiatry
K W PerryF Bymaster

Abstract

The muscarinic agonist xanomeline has been shown to reduce antipsychotic-like behaviors in patients with Alzheimer's disease. Because atypical antipsychotic agents increase dopamine release in prefrontal cortex and induce immediate early gene expression in prefrontal cortex and nucleus accumbens, the effect of xanomeline was determined on these indices. The effect of xanomeline on extracellular levels of monoamines in brain regions was determined using a microdialysis technique, and changes in expression of the immediate early genes c-fos and zif/268 in brain regions were evaluated using in situ hybridization histochemistry. Xanomeline increased extracellular levels of dopamine in prefrontal cortex and nucleus accumbens but not in striatum. Xanomeline increased expression of c-fos and zif/268 in prefrontal cortex and nucleus accumbens. There was no change in immediate early gene expression in striatum. Xanomeline increased extracellular levels of dopamine, which is similar to the effects of the atypical antipsychotics clozapine and olanzapine. The regional pattern of immediate early gene expression induced by xanomeline resembled that of atypical antipsychotic agents. Based on the antipsychotic-like activity of xanomeline in Al...Continue Reading

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Citations

Mar 22, 2005·Psychopharmacology·Oliver FreudenreichDonald C Goff
Sep 4, 2008·Psychopharmacology·Cherrie Galletly
Dec 4, 2003·Progress in Neuro-psychopharmacology & Biological Psychiatry·Frank P BymasterDavid L Mckinzie
Oct 1, 2011·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Carrie K JonesMichael Bubser
Aug 3, 2013·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Marla L WattChristian C Felder
Jun 23, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Gregory J DigbyP Jeffrey Conn
Oct 10, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Carrie K JonesP Jeffrey Conn
Jan 21, 2014·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Nellie E ByunCarrie K Jones
Apr 18, 2003·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Maibritt B AndersenThomas Werge
Dec 6, 2006·Molecular Psychiatry·T J RaedlerB Dean
Dec 22, 2020·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Caterina MontaniChristian Felder
Apr 22, 2021·Neurotoxicology·Yasser A KhadrawyHaitham S Mohammed

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