CoChat
Sign Up
Cited by 7Attention Deficit Hyperactivity DisorderNeuroscience and Neuropharmacology ResearchNeurotransmitter Receptor Influence on Behavior

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

Open access
García-Avilés, Álvaro, Albert-Gascó, Héctor, Arnal-Vicente, Isabel, Elhajj, Ebtisam, Sanjuan-Arias, Julio, Sanchez-Perez, Ana María, Olucha-Bordonau, Francisco·2015·Frontiers in Neuroanatomy
DOI 10.3389/fnana.2015.00033PMC PMC4369875
Open this paper in CoChat — free accountOpen PDF

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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.3389/fnana.2015.00033

Cites

5 of 5 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 64

  1. Abikoff H. Hechtman L. Klein R. G. Weiss G. Fleiss K. Etcovitch J.. (2004). Symptomatic improvement in children with ADHD treated with long-term methylphenidate and multimodal psychosocial treatment. J. Am. Acad. Child Adolesc. Psychiatry 43, 802– 811. 10.1097/01.chi.0000128791.10014.ac 15213581 · DOI
  2. Allen J. K. Wilkinson M. Soo E. C. Hui J. P. M. Chase T. D. Carrey N. (2010). Chronic low dose Adderall XR® down-regulates cfos expression in infantile and prepubertal rat striatum and cortex. Neuroscience 169, 1901– 1912. 10.1016/j.neuroscience.2010.06.029 20600661 · DOI
  3. Aoyama T. Kotaki H. Iga T. (1990). Dose-dependent kinetics of methylphenidate enantiomers after oral administration of racemic methylphenidate to rats. J. Pharmacobiodyn. 13, 647– 652. 10.1248/bpb1978.13.647 2095405 · DOI
  4. Apartis E. Poindessous-Jazat F. R. Lamour Y. A. Bassant M. H. (1998). Loss of rhythmically bursting neurons in rat medial septum following selective lesion of septohippocampal cholinergic system. J. Neurophysiol. 79, 1633– 1642. 9535934
  5. Bakhtiar R. Tse F. L. (2003). Toxicokinetic assessment of methylphenidate (Ritalin(R)) in a 13-week oral (gavage) toxicity study in rats using an enantiomeric liquid chromatography/tandem mass spectrometry assay. Rapid Commun. Mass Spectrom. 17, 2160– 2162. 10.1002/rcm.1167 12955748 · DOI
  6. Berridge C. W. Devilbiss D. M. (2011). Psychostimulants as cognitive enhancers: the prefrontal cortex, catecholamines and attention-deficit/hyperactivity disorder. Biol. Psychiatry 69, e101– e111. 10.1016/j.biopsych.2010.06.023 20875636 PMC3012746 · DOI · Paper page
  7. Biederman J. (2006). Introduction: new developments in the treatment of attention-deficit/hyperactivity disorder. J. Clin. Psychiatry 67(Suppl. 8), 4– 6. 16961423
  8. Biederman J. Faraone S. V. (2005). Attention-deficit hyperactivity disorder. Lancet 366, 237– 248. 10.1016/S0140-6736(05)66915-2 16023516 · DOI · Paper page
  9. Bland B. H. Oddie S. D. (2001). Theta band oscillation and synchrony in the hippocampal formation and associated structures: the case for its role in sensorimotor integration. Behav. Brain Res. 127, 119– 136. 10.1016/s0166-4328(01)00358-8 11718888 · DOI · Paper page
  10. Brandner C. Schenk F. (1998). Septal lesions impair the acquisition of a cued place navigation task: attentional or memory deficit? Neurobiol. Learn. Mem. 69, 106– 125. 10.1006/nlme.1997.3814 9619991 · DOI
  11. Brandon C. L. Marinelli M. Baker L. K. White F. J. (2001). Enhanced reactivity and vulnerability to cocaine following methylphenidate treatment in adolescent rats. Neuropsychopharmacology 25, 651– 661. 10.1016/s0893-133x(01)00281-0 11682248 · DOI · Paper page
  12. Chase T. D. Carrey N. Brown R. E. Wilkinson M. (2005). Methylphenidate regulates c-fos and fosB expression in multiple regions of the immature rat brain. Brain Res. Dev. Brain Res. 156, 1– 12. 10.1016/j.devbrainres.2005.01.011 15862622 · DOI
  13. Chase T. Carrey N. Soo E. Wilkinson M. (2007). Methylphenidate regulates activity regulated cytoskeletal associated but not brain-derived neurotrophic factor gene expression in the developing rat striatum. Neuroscience 144, 969– 984. 10.1016/j.neuroscience.2006.10.035 17156936 · DOI
  14. Clark R. E. Kuczenski R. Segal D. S. (2007). Escalating dose, multiple binge methamphetamine regimen does not impair recognition memory in rats. Synapse 61, 515– 522. 10.1002/syn.20397 17415795 · DOI
  15. Cragg S. J. Nicholson C. Kume-Kick J. Tao L. Rice M. E. (2001). Dopamine-mediated volume transmission in midbrain is regulated by distinct extracellular geometry and uptake. J. Neurophysiol. 85, 1761– 1771. 11287497
  16. Curran T. Morgan J. I. (1995). Fos: an immediate-early transcription factor in neurons. J. Neurobiol. 26, 403– 412. 10.1002/neu.480260312 7775973 · DOI
  17. Dougherty D. D. Bonab A. A. Spencer T. J. Rauch S. L. Madras B. K. Fischman A. J. (1999). Dopamine transporter density in patients with attention deficit hyperactivity disorder. Lancet 354, 2132– 2133. 10.1016/s0140-6736(99)04030-1 10609822 · DOI · Paper page
  18. Fitch T. E. Sahr R. N. Eastwood B. J. Zhou F. C. Yang C. R. (2006). Dopamine D1/5 receptor modulation of firing rate and bidirectional theta burst firing in medial septal/vertical limb of diagonal band neurons in vivo. J. Neurophysiol. 95, 2808– 2820. 10.1152/jn.01210.2005 16452256 · DOI
  19. Freund T. F. (1989). GABAergic septohippocampal neurons contain parvalbumin. Brain Res. 478, 375– 381. 10.1016/0006-8993(89)91520-5 2924136 · DOI
  20. Gatley S. J. Volkow N. D. Gifford A. N. Fowler J. S. Dewey S. L. Ding Y. S.. (1999). Dopamine-transporter occupancy after intravenous doses of cocaine and methylphenidate in mice and humans. Psychopharmacology (Berl) 146, 93– 100. 10.1007/s002130051093 10485970 · DOI
  21. Gerasimov M. R. Franceschi M. Volkow N. D. Gifford A. Gatley S. J. Marsteller D.. (2000). Comparison between intraperitoneal and oral methylphenidate administration: a microdialysis and locomotor activity study. J. Pharmacol. Exp. Ther. 295, 51– 57. 10991960
  22. Gritti I. Manns I. D. Mainville L. Jones B. E. (2003). Parvalbumin, calbindin, or calretinin in cortically projecting and GABAergic, cholinergic, or glutamatergic basal forebrain neurons of the rat. J. Comp. Neurol. 458, 11– 31. 10.1002/cne.10505 12577320 · DOI
  23. Hajós M. Hoffmann W. E. Robinson D. D. Yu J. H. Hajós-Korcsok E. (2003). Norepinephrine but not serotonin reuptake inhibitors enhance theta and gamma activity of the septo-hippocampal system. Neuropsychopharmacology 28, 857– 864. 12637957
  24. Hajós M. Siok C. J. Hoffmann W. E. Li S. Kocsis B. (2008). Modulation of hippocampal theta oscillation by histamine H3 receptors. J. Pharmacol. Exp. Ther. 324, 391– 398. 10.1124/jpet.107.130070 17940197 · DOI
  25. Hajszan T. Alreja M. Leranth C. (2004). Intrinsic vesicular glutamate transporter 2-immunoreactive input to septohippocampal parvalbumin-containing neurons: novel glutamatergic local circuit cells. Hippocampus 14, 499– 509. 10.1002/hipo.10195 15224985 · DOI
  26. Hasselmo M. E. (2005). What is the function of hippocampal theta rhythm?–Linking behavioral data to phasic properties of field potential and unit recording data. Hippocampus 15, 936– 949. 10.1002/hipo.20116 16158423 · DOI · Paper page
  27. Horner W. E. Johnson D. E. Schmidt A. W. Rollema H. (2007). Methylphenidate and atomoxetine increase histamine release in rat prefrontal cortex. Eur. J. Pharmacol. 558, 96– 97. 10.1016/j.ejphar.2006.11.048 17198700 · DOI
  28. Kaufling J. Waltisperger E. Bourdy R. Valera A. Veinante P. Freund-Mercier M. J.. (2010). Pharmacological recruitment of the GABAergic tail of the ventral tegmental area by acute drug exposure. Br. J. Pharmacol. 161, 1677– 1691. 10.1111/j.1476-5381.2010.00984.x 21087442 PMC3010575 · DOI
  29. Kiss J. Maglóczky Z. Somogyi J. Freund T. F. (1997). Distribution of calretinin-containing neurons relative to other neurochemically identified cell types in the medial septum of the rat. Neuroscience 78, 399– 410. 10.1016/s0306-4522(96)00508-8 9145797 · DOI
  30. Kovács K. J. (2008). Measurement of immediate-early gene activation- c-fos and beyond. J. Neuroendocrinol. 20, 665– 672. 10.1111/j.1365-2826.2008.01734.x 18601687 · DOI · Paper page
  31. Krause M. Hoffmann W. E. Hajos M. (2003). Auditory sensory gating in hippocampus and reticular thalamic neurons in anesthetized rats. Biol. Psychiatry 53, 244– 253. 10.1016/s0006-3223(02)01463-4 12559658 · DOI
  32. Kuntsi J. McLoughlin G. Asherson P. (2006). Attention deficit hyperactivity disorder. Neuromolecular Med. 8, 461– 484. 10.1385/NMM:8:4:461 17028370 · DOI
  33. Lee M. G. Chrobak J. J. Sik A. Wiley R. G. Buzsáki G. (1994). Hippocampal theta activity following selective lesion of the septal cholinergic system. Neuroscience 62, 1033– 1047. 10.1016/0306-4522(94)90341-7 7845584 · DOI
  34. Leranth C. Carpi D. Buzsaki G. Kiss J. (1999). The entorhino-septo-supramammillary nucleus connection in the rat: morphological basis of a feedback mechanism regulating hippocampal theta rhythm. Neuroscience 88, 701– 718. 10.1016/s0306-4522(98)00245-0 10363811 · DOI
  35. Liu Y. Liang X. Ren W. W. Li B. M. (2014). Expression of β1- and β2-adrenoceptors in different subtypes of interneurons in the medial prefrontal cortex of mice. Neuroscience 257, 149– 157. 10.1016/j.neuroscience.2013.10.078 24215978 · DOI
  36. Ma J. Shen B. Stewart L. S. Herrick I. A. Leung L. S. (2002). The septohippocampal system participates in general anesthesia. J. Neurosci. 22: RC200. 11784812 PMC6758657
  37. Miller G. M. Madras B. K. (2002). Polymorphisms in the 3′-untranslated region of human and monkey dopamine transporter genes affect reporter gene expression. Mol. Psychiatry 7, 44– 55. 10.1038/sj.mp.4000921 11803445 · DOI
  38. Miura Y. Ito T. Kadokawa T. (1987). Effects of intraseptally injected dopamine and noradrenaline on hippocampal synchronized theta wave activity in rats. Jpn. J. Pharmacol. 44, 471– 479. 10.1254/jjp.44.471 3682411 · DOI
  39. Nerad L. McNaughton N. (2006). The septal EEG suggests a distributed organization of the pacemaker of hippocampal theta in the rat. Eur. J. Neurosci. 24, 155– 166. 10.1111/j.1460-9568.2006.04902.x 16882013 · DOI
  40. Ohno Y. Okano M. Masui A. Imaki J. Egawa M. Yoshihara C.. (2012). Region-specific elevation of D1 receptor-mediated neurotransmission in the nucleus accumbens of SHR, a rat model of attention deficit/hyperactivity disorder. Neuropharmacology 63, 547– 554. 10.1016/j.neuropharm.2012.04.031 22580374 · DOI
  41. Olucha-Bordonau F. E. Otero-García M. Sánchez-Pérez A. M. Núñez A. Ma S. Gundlach A. L. (2012). Distribution and targets of the relaxin-3 innervation of the septal area in the rat. J. Comp. Neurol. 520, 1903– 1939. 10.1002/cne.23018 22134882 · DOI
  42. Paxinos G. Watson C. (1996). The Rat Brain in Stereotaxic. New York: Coordinates Academic Press.
  43. Perez-Villalba A. Teruel-Marti V. Ruiz-Torner A. Olucha-Bordonau F. (2005). The effect of long context exposure on cued conditioning and c-fos expression in the rat forebrain. Behav. Brain Res. 161, 263– 275. 10.1016/j.bbr.2005.02.028 15922053 · DOI
  44. Polanczyk G. de Lima M. S. Horta B. L. Biederman J. Rohde L. A. (2007). The worldwide prevalence of ADHD: a systematic review and metaregression analysis. Am. J. Psychiatry 164, 942– 948. 10.1176/appi.ajp.164.6.942 17541055 · DOI · Paper page
  45. Risold P. Y. (2004). “ The septal region,” in The Rat Nervous System, ed Paxinos G. (Elsevier: San Diego), 605– 632.
  46. Rivera A. Alberti I. Martín A. B. Narváez J. A. de la Calle A. Moratalla R. (2002). Molecular phenotype of rat striatal neurons expressing the dopamine D5 receptor subtype. Eur. J. Neurosci. 16, 2049– 2058. 10.1046/j.1460-9568.2002.02280.x 12473072 · DOI
  47. Russell V. de Villiers A. Sagvolden T. Lamm M. Taljaard J. (1995). Altered dopaminergic function in the prefrontal cortex, nucleus accumbens and caudate-putamen of an animal model of attention-deficit hyperactivity disorder—the spontaneously hypertensive rat. Brain Res. 676, 343– 351. 10.1016/0006-8993(95)00135-d 7614004 · DOI · Paper page
  48. Sánchez-Camacho C. Peña J. J. González A. (2003). Catecholaminergic innervation of the septum in the frog: a combined immunohistochemical and tract-tracing study. J. Comp. Neurol. 455, 310– 323. 10.1002/cne.10500 12483684 · DOI
  49. Sánchez-Pérez A. M. Arnal-Vicente I. Santos F. N. Pereira C. W. ElMlili N. Sanjuan J.. (2015). Septal projections to nucleus incertus in the rat: bidirectional pathways for modulation of hippocampal function. J. Comp. Neurol. 523, 565– 588. 10.1002/cne.23687 25269409 · DOI
  50. Schenk S. Izenwasser S. (2002). Pretreatment with methylphenidate sensitizes rats to the reinforcing effects of cocaine. Pharmacol. Biochem. Behav. 72, 651– 657. 10.1016/s0091-3057(02)00735-9 12175462 · DOI
  51. Swanson L. W. Cowan W. M. (1979). The connections of the septal region in the rat. J. Comp. Neurol. 186, 621– 655. 10.1002/cne.901860408 15116692 · DOI
  52. Swanson J. M. Volkow N. D. (2002). Pharmacokinetic and pharmacodynamic properties of stimulants: implications for the design of new treatments for ADHD. Behav. Brain Res. 130, 73– 78. 10.1016/s0166-4328(01)00433-8 11864720 · DOI · Paper page
  53. Takeuchi A. Ogino T. Hanafusa K. Morooka T. Oka M. Yorifuji T.. (2013). Inhibitory function and working memory in attention deficit/hyperactivity disorder and pervasive developmental disorders:does a continuous cognitive gradient explain ADHD and PDD traits? Acta Med. Okayama 67, 293– 303. 24145729
  54. Trinh J. V. Nehrenberg D. L. Jacobsen J. P. Caron M. G. Wetsel W. C. (2003). Differential psychostimulant-induced activation of neural circuits in dopamine transporter knockout and wild type mice. Neuroscience 118, 297– 310. 10.1016/s0306-4522(03)00165-9 12699766 · DOI · Paper page
  55. Vertes R. P. Kocsis B. (1997). Brainstem-diencephalo-septohippocampal systems controlling the theta rhythm of the hippocampus. Neuroscience 81, 893– 926. 9330355
  56. Volkow N. D. Wang G. J. Newcorn J. Telang F. Solanto M. V. Fowler J. S.. (2007). Depressed dopamine activity in caudate and preliminary evidence of limbic involvement in adults with attention-deficit/hyperactivity disorder. Arch. Gen. Psychiatry 64, 932– 940. 10.1001/archpsyc.64.8.932 17679638 · DOI · Paper page
  57. Walsh T. J. Gandhi C. Stackman R. W. (1998). Reversible inactivation of the medial septum or nucleus basalis impairs working memory in rats: a dissociation of memory and performance. Behav. Neurosci. 112, 1114– 1124. 10.1037//0735-7044.112.5.1114 9829789 · DOI
  58. Wang X. J. (2002). Pacemaker neurons for the theta rhythm and their synchronization in the septohippocampal reciprocal loop. J. Neurophysiol. 87, 889– 900. 11826054
  59. Wargin W. Patrick K. Kilts C. Gualtieri C. T. Ellington K. Mueller R. A.. (1983). Pharmacokinetics of methylphenidate in man, rat and monkey. J. Pharmacol. Exp. Ther. 226, 382– 386. 6410043
  60. Wu M. Hajszan T. Xu C. Leranth C. Alreja M. (2004). Group I metabotropic glutamate receptor activation produces a direct excitation of identified septohippocampal cholinergic neurons. J. Neurophysiol. 92, 1216– 1225. 10.1152/jn.00180.2004 15044519 · DOI
  61. Yoder R. M. Pang K. C. (2005). Involvement of GABAergic and cholinergic medial septal neurons in hippocampal theta rhythm. Hippocampus 15, 381– 392. 10.1002/hipo.20062 15630696 · DOI
  62. Zarrindast M. R. Ardjmand A. Ahmadi S. Rezayof A. (2012). Activation of dopamine D1 receptors in the medial septum improves scopolamine-induced amnesia in the dorsal hippocampus. Behav. Brain Res. 229, 68– 73. 10.1016/j.bbr.2011.12.033 22226623 · DOI
  63. Zetterström T. Sharp T. Collin A. K. Ungerstedt U. (1988). In vivo measurement of extracellular dopamine and DOPAC in rat striatum after various dopamine-releasing drugs; implications for the origin of extracellular DOPAC. Eur. J. Pharmacol. 148, 327– 334. 10.1016/0014-2999(88)90110-0 3384000 · DOI
  64. Zhu N. Weedon J. Dow-Edwards D. L. (2007). Oral methylphenidate improves spatial learning and memory in pre- and periadolescent rats. Behav. Neurosci. 121, 1272– 1279. 10.1037/0735-7044.121.6.1272 18085880 · DOI

Cited by

Sorted by citations

Authors
García-Avilés, Ã., Albert-Gascó, H., Arnal-Vicente, I., Elhajj, E., Sanjuan-Arias, J., Sanchez-Perez, A. M., & Olucha-Bordonau, F.
Affiliations
  • Universitat de València (ES)
  • Alexandria University (EG)
  • Universitat Jaume I (ES)
Corresponding author
Olucha-Bordonau, Francisco
ORCID
Olucha-Bordonau, Francisco
Venue
Frontiers in Neuroanatomy
Publisher
Frontiers Media SA
Published
2015-03-23
Volume
9
Pages
33-33
ISSN
1662-5129 (ISSN-L)
DOI
10.3389/fnana.2015.00033
PMC
PMC4369875
OpenAlex
W1972224501
Cited by
7
References
5
Citations by year
2026: 1 · 2022: 1 · 2021: 1 · 2020: 2 · 2019: 1 · 2015: 1
FWCI
0.25
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Frontiers in Neuroanatomy (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (publishedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Repositori UJI (Universitat Jaume I) (submittedVersion, cc-by-sa)
Funders
Universitat de València
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
methylphenidate, calretinin, medial septum, septohippocampal pathway, Fos expression, attention deficit hyperactivity disorder, dopamine, tyrosine hydroxylase, choline acetyltransferase, parvalbumin, calbindin, hippocampal theta rhythm

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review