Maximizing the effect of an α7 nicotinic receptor PAM in a mouse model of schizophrenia-like sensory inhibition deficits

Brain Research
Karen E StevensJerry A Stitzel

Abstract

Positive allosteric modulators (PAMs) for the α7 nicotinic receptor hold promise for the treatment of sensory inhibition deficits observed in schizophrenia patients. Studies of these compounds in the DBA/2 mouse, which models the schizophrenia-related deficit in sensory inhibition, have shown PAMs to be effective in improving the deficit. However, the first published clinical trial of a PAM for both sensory inhibition deficits and related cognitive difficulties failed, casting a shadow on this therapeutic approach. The present study used both DBA/2 mice, and C3H Chrna7 heterozygote mice to assess the ability of the α7 PAM, PNU-120596, to improve sensory inhibition. Both of these strains of mice have reduced hippocampal α7 nicotinic receptor numbers and deficient sensory inhibition similar to schizophrenia patients. Low doses of PNU-120596 (1 or 3.33mg/kg) were effective in the DBA/2 mouse but not the C3H Chrna7 heterozygote mouse. Moderate doses of the selective α7 nicotinic receptor agonist, choline chloride (10 or 33mg/kg), were also ineffective in improving sensory inhibition in the C3H Chrna7 heterozygote mouse. However, combining the lowest doses of both PNU-120596 and choline chloride in this mouse model did improve senso...Continue Reading

References

Nov 1, 1977·Archives of General Psychiatry·P L McGeer, E G McGeer
Aug 1, 1996·Biological Psychiatry·H T NagamotoR Freedman
Aug 1, 1996·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·K E StevensG M Rose
Jun 5, 1998·Schizophrenia Bulletin·L E AdlerR Freedman
Jul 8, 1999·Biological Psychiatry·L E AdlerM C Waldo
Apr 20, 2000·European Journal of Pharmacology·S LeonardR Freedman
May 17, 2000·American Journal of Medical Genetics·R FreedmanS Leonard
Aug 17, 2001·Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco·S Leonard, D Bertrand
Aug 18, 2001·Pharmacology, Biochemistry, and Behavior·K E StevensA C Collins
Feb 14, 2002·Pharmacology, Biochemistry, and Behavior·S LeonardR Freedman
Apr 3, 2002·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Sudabeh Shirazi-SouthallGeorge G Nomikos
May 29, 2003·Current Drug Targets. CNS and Neurological Disorders·J K SimoskyR Freedman
May 13, 2004·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Josette G HarrisRobert Freedman
Nov 9, 2004·Schizophrenia Research·Michael F GreenRobert K Heaton
Feb 25, 2006·Biological Psychiatry·Kayla L MetzgerSteven J Siegel
Jun 7, 2006·Archives of General Psychiatry·Ann OlincyRobert Freedman
Jan 29, 2008·Recent Patents on CNS Drug Discovery·Ramin FaghihMurali Gopalakrishnan
Jul 17, 2010·The American Journal of Psychiatry·Ashley K SmithJosé M Cañive
Jul 19, 2011·Pharmacology, Biochemistry, and Behavior·Kristin M Wildeboer-Andrud, Karen E Stevens
Oct 1, 2011·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Carrie K JonesMichael Bubser
Nov 15, 2012·Schizophrenia Research·Eva María Sánchez-MorlaCelso Arango
Dec 13, 2012·Expert Opinion on Therapeutic Targets·Tanya L Wallace, Daniel Bertrand
Apr 18, 2013·Schizophrenia Research·Jason SmucnyJason R Tregellas
Feb 18, 2014·European Journal of Pharmacology·Victor V Uteshev

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Citations

Aug 2, 2015·Biochemical Pharmacology·Alvin V TerryCaterina M Hernandez
Feb 16, 2017·British Journal of Pharmacology·Jingyi Wang, Jon Lindstrom
Aug 24, 2018·Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco·Alvin V Terry, Patrick M Callahan

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