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Front Neuroanat. 2015 Mar 23;9:33. doi: 10.3389/fnana.2015.00033. eCollection 2015.

Acute oral administration of low doses of methylphenidate targets calretinin neurons in the rat septal area.

Frontiers in neuroanatomy

Álvaro García-Avilés, Héctor Albert-Gascó, Isabel Arnal-Vicente, Ebtisam Elhajj, Julio Sanjuan-Arias, Ana María Sanchez-Perez, Francisco Olucha-Bordonau

Affiliations

  1. Departamento de Medicina, Facultad de Ciencias de la Salud, Universitat Jaume I Castellón, Spain.
  2. CIBERSAM, INCLIVA, Unidad de Psiquiatría, Departamento Medicina, Facultad Medicina, Universitat de Valencia Valencia, Spain.
  3. Faculty of Science, University of Alexandria Alexandria, Egypt.

PMID: 25852493 PMCID: PMC4369875 DOI: 10.3389/fnana.2015.00033

Abstract

Methylphenidate (MPD) is a commonly administered drug to treat children suffering from attention deficit hyperactivity disorder (ADHD). Alterations in septal driven hippocampal theta rhythm may underlie attention deficits observed in these patients. Amongst others, the septo-hippocampal connections have long been acknowledged to be important in preserving hippocampal function. Thus, we wanted to ascertain if MPD administration, which improves attention in patients, could affect septal areas connecting with hippocampus. We used low and orally administered MPD doses (1.3, 2.7 and 5 mg/Kg) to rats what mimics the dosage range in humans. In our model, we observed no effect when using 1.3 mg/Kg MPD; whereas 2.7 and 5 mg/Kg induced a significant increase in c-fos expression specifically in the medial septum (MS), an area intimately connected to the hippocampus. We analyzed dopaminergic areas such as nucleus accumbens and striatum, and found that only 5 mg/Kg induced c-fos levels increase. In these areas tyrosine hydroxylase correlated well with c-fos staining, whereas in the MS the sparse tyrosine hydroxylase fibers did not overlap with c-fos positive neurons. Double immunofluorescence of c-fos with neuronal markers in the septal area revealed that co-localization with choline acethyl transferase, parvalbumin, and calbindin with c-fos did not change with MPD treatment; whereas, calretinin and c-fos double labeled neurons increased after MPD administration. Altogether, these results suggest that low and acute doses of methylphenidate primary target specific populations of caltretinin medial septal neurons.

Keywords: ADHD; calcium binding proteins; catecholamines; methylphenidate; theta rhythm

References

  1. Neuroscience. 2007 Feb 9;144(3):969-84 - PubMed
  2. Arch Gen Psychiatry. 1995 Jun;52(6):456-63 - PubMed
  3. J Pharmacol Exp Ther. 1983 Aug;226(2):382-6 - PubMed
  4. J Comp Neurol. 2012 Jun 15;520(9):1903-39 - PubMed
  5. Acta Med Okayama. 2013;67(5):293-303 - PubMed
  6. J Pharmacol Exp Ther. 2008 Jan;324(1):391-8 - PubMed
  7. Lancet. 2005 Jul 16-22;366(9481):237-48 - PubMed
  8. Rapid Commun Mass Spectrom. 2003;17(18):2160-2 - PubMed
  9. Biol Psychiatry. 2011 Jun 15;69(12):e101-11 - PubMed
  10. Hippocampus. 2004;14(4):499-509 - PubMed
  11. Brain Res. 1995 Apr 10;676(2):343-51 - PubMed
  12. Neuroscience. 2014 Jan 17;257:149-57 - PubMed
  13. Neuroscience. 2010 Sep 15;169(4):1901-12 - PubMed
  14. J Clin Psychiatry. 2006;67 Suppl 8:4-6 - PubMed
  15. Neuroscience. 1997 May;78(2):399-410 - PubMed
  16. Lancet. 1999 Dec 18-25;354(9196):2132-3 - PubMed
  17. Eur J Neurosci. 2002 Dec;16(11):2049-58 - PubMed
  18. Neuroscience. 1999;88(3):701-18 - PubMed
  19. J Neurosci. 2002 Jan 15;22(2):RC200 - PubMed
  20. Eur J Neurosci. 2006 Jul;24(1):155-66 - PubMed
  21. Neuropharmacology. 2012 Sep;63(4):547-54 - PubMed
  22. Br J Pharmacol. 2010 Dec;161(8):1677-91 - PubMed
  23. Hippocampus. 2005;15(3):381-92 - PubMed
  24. J Comp Neurol. 2003 Jan 13;455(3):310-23 - PubMed
  25. Hippocampus. 2005;15(7):936-49 - PubMed
  26. Biol Psychiatry. 2006 Nov 15;60(10):1111-20 - PubMed
  27. J Comp Neurol. 2003 Mar 24;458(1):11-31 - PubMed
  28. Neuropsychopharmacology. 2001 Nov;25(5):651-61 - PubMed
  29. Neuroscience. 2003;118(2):297-310 - PubMed
  30. Neuromolecular Med. 2006;8(4):461-84 - PubMed
  31. J Neurosci. 2002 Aug 15;22(16):7264-71 - PubMed
  32. J Neurophysiol. 2002 Feb;87(2):889-900 - PubMed
  33. J Pharmacobiodyn. 1990 Oct;13(10):647-52 - PubMed
  34. Synapse. 2007 Jul;61(7):515-22 - PubMed
  35. Mol Psychiatry. 2002;7(1):44-55 - PubMed
  36. Behav Brain Res. 2012 Apr 1;229(1):68-73 - PubMed
  37. J Comp Neurol. 2015 Mar 1;523(4):565-88 - PubMed
  38. Brain Res Dev Brain Res. 2005 Apr 21;156(1):1-12 - PubMed
  39. J Pharmacol Exp Ther. 2000 Oct;295(1):51-7 - PubMed
  40. Behav Brain Res. 2001 Dec 14;127(1-2):119-36 - PubMed
  41. J Neurobiol. 1995 Mar;26(3):403-12 - PubMed
  42. J Neurophysiol. 2006 May;95(5):2808-20 - PubMed
  43. Neuroscience. 1994 Oct;62(4):1033-47 - PubMed
  44. Neurobiol Learn Mem. 1998 Mar;69(2):106-25 - PubMed
  45. Biol Psychiatry. 2003 Feb 1;53(3):244-53 - PubMed
  46. Pharmacol Biochem Behav. 2002 Jun;72(3):651-7 - PubMed
  47. Arch Gen Psychiatry. 2007 Aug;64(8):932-40 - PubMed
  48. Eur J Pharmacol. 2007 Mar 8;558(1-3):96-7 - PubMed
  49. Brain Res. 1989 Jan 30;478(2):375-81 - PubMed
  50. Am J Psychiatry. 2007 Jun;164(6):942-8 - PubMed
  51. Cell Tissue Res. 1978 Jul 10;190(3):383-407 - PubMed
  52. Behav Brain Res. 2002 Mar 10;130(1-2):73-8 - PubMed
  53. Neuroscience. 1997 Dec;81(4):893-926 - PubMed
  54. Jpn J Pharmacol. 1987 Aug;44(4):471-9 - PubMed
  55. Psychopharmacology (Berl). 1999 Sep 1;146(1):93-100 - PubMed
  56. Behav Neurosci. 2007 Dec;121(6):1272-9 - PubMed
  57. J Neurophysiol. 1998 Apr;79(4):1633-42 - PubMed
  58. J Neurophysiol. 2004 Aug;92 (2):1216-25 - PubMed
  59. J Neurophysiol. 2001 Apr;85(4):1761-71 - PubMed
  60. J Am Acad Child Adolesc Psychiatry. 2004 Jul;43(7):802-11 - PubMed
  61. Eur J Pharmacol. 1988 Apr 13;148(3):327-34 - PubMed
  62. J Comp Neurol. 1979 Aug 15;186(4):621-55 - PubMed
  63. J Neuroendocrinol. 2008 Jun;20(6):665-72 - PubMed
  64. Neuropsychopharmacology. 2003 May;28(5):857-64 - PubMed
  65. Behav Brain Res. 2005 Jun 20;161(2):263-75 - PubMed
  66. Behav Neurosci. 1998 Oct;112(5):1114-24 - PubMed

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