Display options
Share it on

Clin Psychopharmacol Neurosci. 2012 Apr;10(1):25-33. doi: 10.9758/cpn.2012.10.1.25. Epub 2012 Apr 30.

Altered neuronal markers following treatment with mood stabilizer and antipsychotic drugs indicate an increased likelihood of neurotransmitter release.

Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology

Elizabeth Scarr, Brian Dean

Affiliations

  1. Department of Psychiatry, Rebecca L. Cooper Research Laboratories, The Mental Health Research Institute, Melbourne Brain Centre, The University of Melbourne, Parkville, Australia.

PMID: 23429852 PMCID: PMC3569157 DOI: 10.9758/cpn.2012.10.1.25

Abstract

OBJECTIVE: Given the ability of mood stabilizers and antipsychotics to promote cell proliferation, we wanted to determine the effects of these drugs on neuronal markers previously reported to be altered in subjects with psychiatric disorders.

METHODS: Male Sprauge-Dawley rats were treated with vehicle (ethanol), lithium (25.5 mg per day), haloperidol (0.1 mg/kg), olanzapine (1.0 mg/kg) or a combination of lithium and either of the antipsychotic drugs for 28 days. Levels of cortical synaptic (synaptosomal associated protein-25, synaptophysin, vesicle associated protein and syntaxin) and structural (neural cell adhesion molecule and alpha-synuclein) proteins were determined in each treatment group using Western blots.

RESULTS: Compared to the vehicle treated group; animals treated with haloperidol had greater levels of synaptosomal associated protein-25 (p<0.01) and neural cell adhesion molecule (p<0.05), those treated with olanzapine had greater levels of synaptophysin (p<0.01) and syntaxin (p<0.01). Treatment with lithium alone did not affect the levels of any of the proteins. Combining lithium and haloperidol resulted in greater levels of synaptophysin (p<0.01), synaptosomal associated protein-25 (p<0.01) and neural cell adhesion molecule (p<0.01). The combination of lithium and olanzapine produced greater levels of synaptophysin (p<0.01) and alpha-synuclein (p<0.05).

CONCLUSION: Lithium alone had no effect on the neuronal markers. However, haloperidol and olanzapine affected different presynaptic markers. Combining lithium with olanzapine additionally increased alpha-synuclein. These drug effects need to be taken into account by future studies examining presynaptic and neuronal markers in tissue from subjects with psychiatric disorders.

Keywords: Antipsychotic agents; Lithium; Nerve tissue proteins; Neural cell adhesion molecules; SNARE proteins

References

  1. Eur J Neurosci. 2007 Sep;26(6):1509-20 - PubMed
  2. Arch Gen Psychiatry. 1997 Jun;54(6):559-66 - PubMed
  3. EMBO J. 1995 Jan 16;14(2):224-31 - PubMed
  4. Bipolar Disord. 2006 Apr;8(2):133-43 - PubMed
  5. Neuropsychopharmacology. 2009 Mar;34(4):987-98 - PubMed
  6. Neuron. 2000 Jan;25(1):239-52 - PubMed
  7. J Neurosci. 1995 Jan;15(1 Pt 2):511-9 - PubMed
  8. Trends Neurosci. 1998 Jun;21(6):249-54 - PubMed
  9. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350-4 - PubMed
  10. J Pharmacol Exp Ther. 2003 May;305(2):625-31 - PubMed
  11. Biol Psychiatry. 2005 May 1;57(9):1041-51 - PubMed
  12. Neuropsychopharmacology. 2010 Apr;35(5):1226-38 - PubMed
  13. J Neurobiol. 1995 Mar;26(3):437-46 - PubMed
  14. Aust N Z J Psychiatry. 2000 Aug;34(4):560-9 - PubMed
  15. Psychiatry Res. 2010 Jul 30;178(2):374-80 - PubMed
  16. J Psychopharmacol. 2005 Jul;19(4):402-7 - PubMed
  17. Biol Psychiatry. 2010 Feb 1;67(3):208-16 - PubMed
  18. Neurobiol Dis. 2010 Mar;37(3):596-603 - PubMed
  19. World J Biol Psychiatry. 2002 Jul;3(3):125-32 - PubMed
  20. J Neurochem. 2000 Jun;74(6):2365-72 - PubMed
  21. Mol Psychiatry. 2000 Mar;5(2):142-9 - PubMed
  22. Expert Rev Neurother. 2008 Jan;8(1):93-110 - PubMed
  23. Neuropsychobiology. 2001;44(4):187-91 - PubMed
  24. Mol Psychiatry. 1997 Jul;2(4):322-9 - PubMed
  25. Neuroreport. 2001 Oct 29;12(15):3257-62 - PubMed
  26. J Neurochem. 2000 Oct;75(4):1729-34 - PubMed
  27. J Mol Neurosci. 2003 Apr;20(2):83-92 - PubMed
  28. Trends Pharmacol Sci. 2008 Sep;29(9):445-53 - PubMed
  29. Expert Rev Neurother. 2009 Jan;9(1):73-86 - PubMed
  30. Bipolar Disord. 2000 Sep;2(3 Pt 2):261-8 - PubMed
  31. EMBO J. 2004 Nov 10;23(22):4506-16 - PubMed
  32. Biol Psychiatry. 2004 Oct 15;56(8):570-80 - PubMed
  33. Psychiatr Serv. 2002 Oct;53(10):1212 - PubMed
  34. Brain Res Mol Brain Res. 1998 Oct 30;61(1-2):238-42 - PubMed
  35. Neuropsychopharmacology. 2004 Jul;29(7):1230-8 - PubMed
  36. Expert Rev Neurother. 2009 Jan;9(1):109-36 - PubMed
  37. J Neurosci. 2002 Oct 15;22(20):8797-807 - PubMed
  38. Clin Ther. 2005;27 Suppl A:S16-24 - PubMed
  39. Bipolar Disord. 2005 Oct;7(5):449-55 - PubMed
  40. Science. 2010 Sep 24;329(5999):1663-7 - PubMed
  41. J Neurosci. 2000 May 1;20(9):3214-20 - PubMed
  42. Neuropsychopharmacology. 2008 Jan;33(1):141-65 - PubMed
  43. J Neurosci Res. 2004 Mar 15;75(6):854-60 - PubMed
  44. J Neurosci. 2004 Feb 25;24(8):1852-64 - PubMed
  45. Schizophr Res. 2009 Jul;112(1-3):65-71 - PubMed
  46. J Nerv Ment Dis. 2008 Dec;196(12):884-90 - PubMed
  47. Biol Psychiatry. 1998 Feb 15;43(4):239-43 - PubMed
  48. Psychopharmacology (Berl). 1992;106(1):131-5 - PubMed
  49. Mol Psychiatry. 2002;7(6):571-8 - PubMed
  50. Proteomics. 2008 Dec;8(23-24):5097-107 - PubMed
  51. Int J Neuropsychopharmacol. 2008 Aug;11(5):591-5 - PubMed
  52. Nature. 1993 Mar 25;362(6418):318-24 - PubMed
  53. Neuron. 2000 Apr;26(1):207-17 - PubMed
  54. Arch Gen Psychiatry. 2002 Jan;59(1):62-9 - PubMed
  55. Cereb Cortex. 2002 Apr;12(4):349-56 - PubMed
  56. Neuroscience. 1997 May;78(1):99-110 - PubMed

Publication Types