CoChat
Sign Up
Cited by 37Neurotransmitter Receptor Influence on BehaviorAttention Deficit Hyperactivity DisorderNeuroscience and Neuropharmacology Research

Acute and chronic dose–response effect of methylphenidate on ventral tegmental area neurons correlated with animal behavior

Open access
Jones, Zachary, Dafny, Nachum·2014·Journal of Neural Transmission
DOI 10.1007/s00702-013-1101-2PMC PMC4743876
Open this paper in CoChat — free account

Abstract

Methylphenidate (MPD) is used to treat ADHD and as a cognitive enhancement and recreationally. MPD's effects are not fully understood. One of the sites of psychostimulant action is the ventral tegmental area (VTA). The VTA neuronal activity was recorded from freely behaving rats using a wireless system. 51 animals were divided into groups: saline, 0.6, 2.5, and 10.0 mg/kg MPD. The same repetitive MPD dose can elicit either behavioral sensitization or tolerance; thus the evaluation of the VTA neuronal activity was based on the animals' behavioral response to chronic MPD exposure: animals exhibiting behavioral tolerance or sensitization. Acute MPD elicits dose-related increases in behavioral activity. About half of the animals exhibited behavioral sensitization or tolerance to each of the MPD doses. 361 units were recorded from the VTA and exhibited similar spike shape on experimental day 1 (ED1) and on ED10. 71, 84, and 79 % of VTA units responded to acute 0.6, 2.5, and 10.0 mg/kg MPD, respectively. The neuronal baseline activity at ED10 was significantly modified in 94, 95, and 100 % of VTA units following 0.6, 2.5 and 10.0 mg/kg MPD, respectively. Following chronic MPD exposure, 91, 98, and 100 % exhibit either electrophysiological tolerance or sensitization of 0.6, 2.6, or 10.0 mg/kg MPD, respectively. In conclusion, the chronic administration of the same dose of MPD caused some animals to exhibit behavioral sensitization and other animals to exhibit tolerance. The VTA units recorded from animals exhibiting behavioral sensitization responded significantly differently to MPD from animals that exhibited behavioral tolerance.

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 · 10.1007/s00702-013-1101-2

Cites

4 of 4 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?

  • Chronic abuse of MPH induces the expression of inflammatory cytokines, such as TNFα and IL-1β.

    “The chronic abuse of MPH also induces the expression of inflammatory cytokines, such as TNFα and IL-1β [148, 196, 197].”

    From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [196]

    The Introduction and Discussion describe biochemical changes, VTA neuronal activity, and behavioral responses to repeated methylphenidate, but do not address inflammatory cytokines. Searches for TNFα, IL-1β, and cytokine expression found no passage supporting the attributed claim. The indexed copy provides no page numbers. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

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: 94

  1. Algahim MF Yang PB Wilcox VT Burau KD Swann AC Dafny N Prolonged methylphenidate treatment alters the behavioral diurnal activity pattern of adult male Sprague-Dawley rats. Pharmacol. Biochem. Behav 2009 92 93 99 19028517
  2. Askenasy EP Taber KH Yang PB Dafny N Methylphenidate (Ritalin): behavioral studies in the rat. Int. J. Neurosci 2007 117 757 794 17454243
  3. Barron E Yang PB Swann AC Dafny N Adolescent and adult male spontaneous hyperactive rats (SHR) respond differently to acute and chronic methylphenidate (Ritalin). Int. J. Neurosci 2009 119 40 58 19116830
  4. Beckstead RM Domesick VB Nauta WJ Efferent connections of the substantia nigra and ventral tegmental area in the rat. Brain Res 1979 175 191 217 314832
  5. Bergheim M Yang PB Burau KD Dafny N Adolescent rat circadian activity is modulated by psychostimulants. Brain Res 2012 1431 35 45 22146676 PMC3271788
  6. Bonci A Williams JT A common mechanism mediates long-term changes in synaptic transmission after chronic cocaine and morphine. Neuron 1996 16 631 639 8785060
  7. Challman TD Lipsky JJ Methylphenidate: its pharmacology and uses. Mayo Clin. Proc 2000 75 711 721 10907387
  8. Chao J Nestler EJ Molecular neurobiology of drug addiction. Annu. Rev. Med 2004 55 113 132 14746512
  9. Chong SL Claussen CM Dafny N Nucleus accumbens neuronal activity in freely behaving rats is modulated following acute and chronic methylphenidate administration. Brain Res. Bull 2012 87 445 456 22248440 PMC3295903
  10. Claussen CM Dafny N Acute and chronic methylphenidate modulates the neuronal activity of the caudate nucleus recorded from freely behaving rats. Brain Research Bulletin 2012 87 387 396 22040860
  11. Dafny N Electrophysiological properties of caudate neurons following substantia nigra, motor cortex, and amygdaloid nuclear complex stimulation of the rat. Appl. Neurophysiol 1975 38 259 272 1235772
  12. Dafny N Multiunit recording from medial basal hypothalamus following acute and chronic morphine treatment. Brain Res 1980 190 584 592 7189436
  13. Dafny N The hypothalamus exhibits electrophysiologic evidence for morphine tolerance and dependence. Exp. Neurol 1982 77 66 77 7200913
  14. Dafny N Terkel J Hypothalamic neuronal activity associated with onset of pseudopregnancy in the rat. Neuroendocrinology 1990 51 459 467 2111893
  15. Dafny N Yang PB The role of age, genotype, sex, and route of acute and chronic administration of methylphenidate: a review of its locomotor effects. Brain Res. Bull 2006 68 393 405 16459193
  16. Dietz DM Dietz KC Nestler EJ Russo SJ Molecular mechanisms of psychostimulant-induced structural plasticity. Pharmacopsychiatry 42 Suppl 2009 1 S69 S78 PMC2734446 19434558
  17. Fan D Rich D Holtzman T Ruther P Dalley JW Lopez A Rossi MA Barter JW Salas-Meza D Herwik S Holzhammer T Morizio J Yin HH A wireless multi-channel recording system for freely behaving mice and rats. PLoS. One 2011 6 e22033 21765934 PMC3134473
  18. Garland EJ Intranasal abuse of prescribed methylphenidate. J. Am. Acad. Child Adolesc. Psychiatry 1998 37 1242 1243 9847492
  19. Gatley SJ Volkow ND Gifford AN Fowler JS Dewey SL Ding YS Logan J Dopamine-transporter occupancy after intravenous doses of cocaine and methylphenidate in mice and humans. Psychopharmacology (Berl) 1999 146 93 100 10485970
  20. Gaytan O Ghelani D Martin S Swann A Dafny N Dose response characteristics of methylphenidate on different indices of rats' locomotor activity at the beginning of the dark cycle. Brain Res 1996 727 13 21 8842378
  21. Gaytan O Ghelani D Martin S Swann A Dafny N Methylphenidate: diurnal effects on locomotor and stereotypic behavior in the rat. Brain Res 1997 777 1 12 9449407
  22. Gaytan O Al-rahim S Swann A Dafny N Sensitization to locomotor effects of methylphenidate in the rat. Life Sci 1997 61 L101 L107 9275016
  23. Gaytan O Lewis C Swann A Dafny N Diurnal differences in amphetamine sensitization. Eur J. Pharmacol 1999 374 1 9 10422634
  24. Gaytan O Nason R Alagugurusamy R Swann A Dafny N MK-801 blocks the development of sensitization to the locomotor effects of methylphenidate. Brain Res Bull 2000 51 485 492 10758338
  25. Gerasimov MR Franceschi M Volkow ND Gifford A Gatley SJ Marsteller D Molina PE Dewey SL Comparison between intraperitoneal and oral methylphenidate administration: A microdialysis and locomotor activity study. J. Pharmacol. Exp. Ther 2000 295 51 57 10991960
  26. Grace AA Onn SP Morphology and electrophysiological properties of immunocytochemically identified rat dopamine neurons recorded in vitro. J. Neurosci 1989 9 3463 3481 2795134 PMC6569889
  27. Grace AA Phasic versus tonic dopamine release and the modulation of dopamine system responsivity: a hypothesis for the etiology of schizophrenia. Neuroscience 1991 41 1 24 1676137
  28. Gronier B In vivo electrophysiological effects of methylphenidate in the prefrontal cortex: involvement of dopamine D1 and alpha 2 adrenergic receptors. Eur Neuropsychopharmacol 2011 21 192 204 21146374
  29. Hyman SE Malenka RC Addiction and the brain: the neurobiology of compulsion and its persistence. Nat. Rev. Neurosci 2001 2 695 703 11584307
  30. Izenwasser S Coy AE Ladenheim B Loeloff RJ Cadet JL French D Chronic methylphenidate alters locomotor activity and dopamine transporters differently from cocaine. Eur. J. Pharmacol 1999 373 187 193 10414438
  31. Johnson SW North RA Two types of neurone in the rat ventral tegmental area and their synaptic inputs. J. Physiol 1992 450 455 468 1331427 PMC1176131
  32. Joyce MP Rayport S Mesoaccumbens dopamine neuron synapses reconstructed in vitro are glutamatergic. Neuroscience 2000 99 445 456 11029537
  33. Kalivas PW Duffy P DuMars LA Skinner C Behavioral and neurochemical effects of acute and daily cocaine administration in rats. J. Pharmacol. Exp. Ther 1988 245 485 492 3130474
  34. Kalivas PW Weber B Amphetamine injection into the ventral mesencephalon sensitizes rats to peripheral amphetamine and cocaine. J. Pharmacol. Exp. Ther 1988 245 1095 1102 3385638
  35. Kalivas PW Stewart J Dopamine transmission in the initiation and expression of drug- and stress-induced sensitization of motor activity. Brain Res. Brain Res. Rev 1991 16 223 244 1665095
  36. Kalivas PW Duffy P Time course of extracellular dopamine and behavioral sensitization to cocaine. II. Dopamine perikarya. J. Neurosci 1993 13 276 284 8380850 PMC6576314
  37. Kalivas PW Sorg BA Hooks MS The pharmacology and neural circuitry of sensitization to psychostimulants. Behav. Pharmacol 1993 4 315 334 11224200
  38. Kalivas PW Duffy P D1 receptors modulate glutamate transmission in the ventral tegmental area. J. Neurosci 1995 15 5379 5388 7623160 PMC6577867
  39. Kalivas PW Pierce RC Cornish J Sorg BA A role for sensitization in craving and relapse in cocaine addiction. J. Psychopharmacol 1998 12 49 53 9584968
  40. Kallman WM Isaac W The effects of age and illumination on the dose-response curves for three stimulants. Psychopharmacologia 1975 40 313 318 1144644
  41. Kauer JA Learning mechanisms in addiction: synaptic plasticity in the ventral tegmental area as a result of exposure to drugs of abuse. Annu. Rev. Physiol 2004 66 447 475 14977410
  42. Kelz MB Chen J Carlezon WA Jr. Whisler K Gilden L Beckmann AM Steffen C Zhang YJ Marotti L Self DW Tkatch T Baranauskas G Surmeier DJ Neve RL Duman RS Picciotto MR Nestler EJ Expression of the transcription factor deltaFosB in the brain controls sensitivity to cocaine. Nature 1999 401 272 276 10499584
  43. Kim Y Teylan MA Baron M Sands A Nairn AC Greengard P Methylphenidate-induced dendritic spine formation and DeltaFosB expression in nucleus accumbens. Proc. Natl. Acad. Sci. U. S. A 2009 106 2915 2920 19202072 PMC2650365
  44. Lacroix D Ferron A Electrophysiological effects of methylphenidate on the coeruleo-cortical noradrenergic system in the rat. Eur J. Pharmacol 1988 149 277 285 3409954
  45. Lee MJ Yang PB Wilcox VT Burau KD Swann AC Dafny N Does repetitive Ritalin injection produce long-term effects on SD female adolescent rats? Neuropharmacology 2009 57 201 207 19540860
  46. Lee SS Humphreys KL Flory K Liu R Glass K Prospective association of childhood attention-deficit/hyperactivity disorder (ADHD) and substance use and abuse/dependence: a meta-analytic review. Clin. Psychol. Rev 2011 31 328 341 21382538 PMC3180912
  47. Massello W III Carpenter DA A fatality due to the intranasal abuse of methylphenidate (Ritalin). J. Forensic Sci 1999 44 220 221 9987890
  48. Moratalla R Vallejo M Elibol B Graybiel AM D1-class dopamine receptors influence cocaine-induced persistent expression of Fos-related proteins in striatum. Neuroreport 1996 8 1 5 9051741
  49. Morris JA Gardner MJ Calculating confidence intervals for relative risks (odds ratios) and standardised ratios and rates. Br. Med. J. (Clin. Res Ed) 1988 296 1313 1316 PMC2545775 3133061
  50. Nair-Roberts RG Chatelain-Badie SD Benson E White-Cooper H Bolam JP Ungless MA Stereological estimates of dopaminergic, GABAergic and glutamatergic neurons in the ventral tegmental area, substantia nigra and retrorubral field in the rat. Neuroscience 2008 152 1024 1031 18355970 PMC2575227
  51. Nestler EJ Molecular mechanisms of drug addiction. Neuropharmacology 47 Suppl 2004 1 24 32 15464123
  52. Nestler EJ Is there a common molecular pathway for addiction? Nat. Neurosci 2005 8 1445 1449 16251986
  53. Nestler EJ Review. Transcriptional mechanisms of addiction: role of DeltaFosB. Philos. Trans. R. Soc. Lond B Biol. Sci 2008 363 3245 3255 18640924 PMC2607320
  54. Papla I Filip M Przegalinski E Effect of intra-tegmental microinjections of 5-HT1B receptor ligands on the amphetamine-induced locomotor hyperactivity in rats. Pol. J. Pharmacol 2002 54 351 357 12523488
  55. Paxinos G Watson C The Rat Brain in Stereotaxic Coordinates 1986 6110810
  56. Peakman MC Colby C Perrotti LI Tekumalla P Carle T Ulery P Chao J Duman C Steffen C Monteggia L Allen MR Stock JL Duman RS McNeish JD Barrot M Self DW Nestler EJ Schaeffer E Inducible, brain region-specific expression of a dominant negative mutant of c-Jun in transgenic mice decreases sensitivity to cocaine. Brain Res 2003 970 73 86 12706249
  57. Pert A Neurobiological substrates underlying conditioned effects of cocaine. Adv. Pharmacol 1998 42 991 995 9328064
  58. Perugini M Vezina P Amphetamine administered to the ventral tegmental area sensitizes rats to the locomotor effects of nucleus accumbens amphetamine. J. Pharmacol. Exp. Ther 1994 270 690 696 8071860
  59. Pierce RC Kalivas PW Amphetamine produces sensitized increases in locomotion and extracellular dopamine preferentially in the nucleus accumbens shell of rats administered repeated cocaine. J. Pharmacol. Exp. Ther 1995 275 1019 1029 7473128
  60. Pierce RC Kalivas PW A circuitry model of the expression of behavioral sensitization to amphetamine-like psychostimulants. Brain Res Brain Res Rev 1997 25 192 216 9403138
  61. Podet A Lee MJ Swann AC Dafny N Nucleus accumbens lesions modulate the effects of methylphenidate. Brain Res. Bull 2010 82 293 301 20470871 PMC3935495
  62. Prieto-Gomez B Benitez MT Vazquez-Alvarez AM Yang PB Reyes VC Dafny N Dopaminergic ventral tegmental neurons modulated by methylphenidate. Life Sci 2004 74 1581 1592 14738903
  63. Prieto-Gomez B Vazquez-Alvarez AM Martinez-Pena JL Reyes-Vazquez C Yang PB Dafny N Methylphenidate and amphetamine modulate differently the NMDA and AMPA glutamatergic transmission of dopaminergic neurons in the ventral tegmental area. Life Sci 2005 77 635 649 15921995
  64. Robinson TE Behavioral sensitization: characterization of enduring changes in rotational behavior produced by intermittent injections of amphetamine in male and female rats. Psychopharmacology (Berl) 1984 84 466 475 6441946
  65. Robinson TE Berridge KC The neural basis of drug craving: an incentive-sensitization theory of addiction. Brain Res Brain Res Rev 1993 18 247 291 8401595
  66. Robinson TE Kolb B Persistent structural modifications in nucleus accumbens and prefrontal cortex neurons produced by previous experience with amphetamine. J. Neurosci 1997 17 8491 8497 9334421 PMC6573726
  67. Robinson TE Kolb B Alterations in the morphology of dendrites and dendritic spines in the nucleus accumbens and prefrontal cortex following repeated treatment with amphetamine or cocaine. Eur J. Neurosci 1999 11 1598 1604 10215912
  68. Robison AJ Nestler EJ Transcriptional and epigenetic mechanisms of addiction. Nat. Rev. Neurosci 2011 12 623 637 21989194 PMC3272277
  69. Salek RL Claussen CM Perez A Dafny N Acute and chronic methylphenidate alters prefrontal cortex neuronal activity recorded from freely behaving rats. Eur. J. Pharmacol 2012 679 60 67 22306242 PMC3293368
  70. Scheggi S Leggio B Masi F Grappi S Gambarana C Nanni G Rauggi R De Montis MG Selective modifications in the nucleus accumbens of dopamine synaptic transmission in rats exposed to chronic stress. J. Neurochem 2002 83 895 903 12421362
  71. Seeman P Madras BK Anti-hyperactivity medication: methylphenidate and amphetamine. Mol. Psychiatry 1998 3 386 396 9774771
  72. Seeman P Madras B Methylphenidate elevates resting dopamine which lowers the impulse-triggered release of dopamine: a hypothesis. Behav. Brain Res 2002 130 79 83 11864721
  73. Solanto MV Neuropsychopharmacological mechanisms of stimulant drug action in attention-deficit hyperactivity disorder: a review and integration. Behav. Brain Res 1998 94 127 152 9708845
  74. Spanagel R Herz A Shippenberg TS Opposing tonically active endogenous opioid systems modulate the mesolimbic dopaminergic pathway. Proc. Natl. Acad. Sci. U. S. A 1992 89 2046 2050 1347943 PMC48593
  75. Tang A Wanchoo SJ Swann AC Dafny N Psychostimulant treatment for ADHD is modulated by prefrontal cortex manipulation. Brain Res Bull 2009 80 353 358 19729055
  76. Teo SK Stirling DI Thomas SD Khetani VD Neurobehavioral effects of racemic threo-methylphenidate and its D and L enantiomers in rats. Pharmacol. Biochem. Behav 2003 74 747 754 12543241
  77. Vanderschuren LJ Trezza V Griffioen-Roose S Schiepers OJ Van LN De Vries TJ Schoffelmeer AN Methylphenidate disrupts social play behavior in adolescent rats. Neuropsychopharmacology 2008 33 2946 2956 18305462 PMC2580804
  78. Vezina P Amphetamine injected into the ventral tegmental area sensitizes the nucleus accumbens dopaminergic response to systemic amphetamine: an in vivo microdialysis study in the rat. Brain Res 1993 605 332 337 8386970
  79. Volkow ND Fowler JS Wang G Ding Y Gatley SJ Mechanism of action of methylphenidate: insights from PET imaging studies. J. Atten. Disord. 6 Suppl 2002 1 S31 S43 12685517
  80. Volkow ND Swanson JM Variables that affect the clinical use and abuse of methylphenidate in the treatment of ADHD. Am. J. Psychiatry 2003 160 1909 1918 14594733
  81. Volkow ND Wang GJ Fowler JS Ding YS Imaging the effects of methylphenidate on brain dopamine: new model on its therapeutic actions for attention-deficit/hyperactivity disorder. Biol. Psychiatry 2005 57 1410 1415 15950015
  82. Volz TJ Farnsworth SJ Hanson GR Fleckenstein AE Method development and validation of an in vitro model of the effects of methylphenidate on membrane-associated synaptic vesicles. J. Neurosci. Methods 2009 177 177 182 18992277 PMC2768605
  83. Wanchoo SJ Lee MJ Swann AC Dafny N Bilateral six-hydroxydopamine administration to PFC prevents the expression of behavioral sensitization to methylphenidate. Brain Res 2010 1312 89 100 19932692 PMC4036823
  84. Waterson P Eason K Tutt D Dent M Using HIT to deliver integrated care for the frail elderly in the UK: current barriers and future challenges. Work 41 Suppl 2012 1 4490 4493 22317413
  85. White FJ Kalivas PW Neuroadaptations involved in amphetamine and cocaine addiction. Drug Alcohol Depend 1998 51 141 153 9716936
  86. White SR Yadao CM Characterization of methylphenidate exposures reported to a regional poison control center. Arch. Pediatr. Adolesc. Med 2000 154 1199 1203 11115302
  87. Wolf ME The role of excitatory amino acids in behavioral sensitization to psychomotor stimulants. Prog. Neurobiol 1998 54 679 720 9560846
  88. Yang PB Amini B Swann AC Dafny N Strain differences in the behavioral responses of male rats to chronically administered methylphenidate. Brain Res 2003 971 139 152 12706230
  89. Yang PB Swann AC Dafny N Sensory-evoked potentials recordings from the ventral tegmental area, nucleus accumbens, prefrontal cortex, and caudate nucleus and locomotor activity are modulated in dose-response characteristics by methylphenidate. Brain Res 2006 1073-1074 164 174 16473326
  90. Yang PB Swann AC Dafny N Chronic methylphenidate modulates locomotor activity and sensory evoked responses in the VTA and NAc of freely behaving rats. Neuropharmacology 2006 51 546 556 16824558
  91. Yang PB Swann AC Dafny N Dose-response characteristics of methylphenidate on locomotor behavior and on sensory evoked potentials recorded from the VTA, NAc, and PFC in freely behaving rats. Behav. Brain Funct 2006 2 3 16417623 PMC1360669
  92. Yang PB Swann AC Dafny N Acute and chronic methylphenidate dose-response assessment on three adolescent male rat strains. Brain Res. Bull 2006 71 301 310 17113960 PMC2048685
  93. Yang PB Swann AC Dafny N Chronic administration of methylphenidate produces neurophysiological and behavioral sensitization. Brain Res 2007 1145 66 80 17335781 PMC1902809
  94. Yang PB Atkins KD Dafny N Behavioral sensitization and cross-sensitization between methylphenidate amphetamine, and 3,4-methylenedioxymethamphetamine (MDMA) in female SD rats. Eur J. Pharmacol 2011 661 72 85 21549116 PMC4036816

Cited by

Sorted by citations

Authors
Jones, Z., & Dafny, N.
Affiliations
The University of Texas Health Science Center at Houston (US)
Corresponding author
Dafny, Nachum
ORCID
Venue
Journal of Neural Transmission
Publisher
Springer Science and Business Media LLC
Published
2013-11-20
Volume
121
Issue
3
Pages
327-345
ISSN
  • 0300-9564 (ISSN-L)
  • 1435-1463
DOI
10.1007/s00702-013-1101-2
PMC
PMC4743876
OpenAlex
W2072355718
Cited by
37
References
4
Citations by year
2023: 1 · 2022: 8 · 2021: 2 · 2020: 2 · 2019: 4 · 2018: 2 · 2017: 3 · 2016: 6 · 2015: 7 · 2014: 1 · 2013: 1
FWCI
2.45
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Journal of Neural Transmission (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Institute on Drug Abuse (R01DA027222, DA RO1 027222)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
methylphenidate, ventral tegmental area, neuronal activity, behavioral sensitization, tolerance (pharmacology and immunology), dose-response relationship, psychostimulants, attention deficit hyperactivity disorder, chronic drug exposure, single-unit recording
MeSH terms
Action Potentials, Central Nervous System Stimulants, Analysis of Variance, Animals, Behavior, Animal, Dose-Response Relationship, Drug, Male, Methylphenidate, Motor Activity, Neurons, Statistics as Topic, Time Factors, Rats, Sprague-Dawley, Ventral Tegmental Area, Rats

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