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Repetitive methylphenidate administration modulates the diurnal behavioral activity pattern of adult female SD rats

  • Biological Child and Adolescent Psychiatry - Original Article
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Abstract

Diurnal rhythms influence many of the physiological processes that act to maintain homeostasis of the body in response to different environmental changes. Thus, disturbances in diurnal rhythms can lead to various physiological complications. Repeated exposure to psychostimulants may cause long-term effects by disturbing diurnal rhythms. The aim of the present study is to use the open field assay to determine whether repeated exposure to the psychostimulant methylphenidate (MPD) changes diurnal locomotor activity patterns of female adult Sprague-Dawley (SD) rats. As much as 31 female adult SD rats were divided into four groups. On experimental day (ED) 1, all groups were given an injection of saline. On ED 2–7, animals were injected once a day with either saline, or 0.6 mg/kg MPD, or 2.5 mg/kg MPD, or 10 mg/kg MPD depending on the group. On ED 8–10, no injections were given (washout period). On ED 11, animals were treated as they were on ED 2–7. Locomotor movements were recorded using a computerized animal activity monitoring system. The horizontal activity (HA), total distance traveled (TDT), and number of stereotypies (NOS) were analyzed by cosine curve statistical analysis (CCSA) test. The HA and TDT diurnal rhythm activity patterns of ED 2, 7, 8, and 11 were significantly different (p < 0.05) from the control recording of ED 1 according to the CCSA test. The observation obtained in this study suggests that repeated administration of MPD (all doses tested) is able to change diurnal locomotor patterns, which indicates that chronic MPD treatment exerts long-term effects.

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References

  • Algahim MF, Yang PB, Wilcox VT, Burau KD, Swann AC, Dafny N (2009) Chronic methylphenidate modulates the circadian activity pattern of adolescent SD rats. In: Gordon SM, Mitchell AE (eds) Attention Deficit Hyperactivity Disorder (ADHD), pp 581–598

  • Anckarsater H, Stahlberg O, Larson T, Hakansson C, Jutblad SB, Niklasson L, Nydén A, Wentz E, Westergren S, Cloninger CR, Gillberg C, Rastam M (2006) The impact of ADHD and autism spectrum disorders on temperament, character, and personality development. Am J Psychiatry 163:1239–1244

    Article  PubMed  Google Scholar 

  • Andersen SL, Teicher MH (2000) Sex differences in dopamine receptors and their relevance to ADHD. Neurosci Biobehav Rev 24:137–141

    Article  PubMed  CAS  Google Scholar 

  • Askenasy EP, Taber KH, Yang PB, Dafny N (2007) Methylphenidate (Ritalin): behavioral studies in the rat. Int J Neurosci 117:757–794

    Article  PubMed  CAS  Google Scholar 

  • Becker JB, Molenda H, Hummer DL (2001) Gender differences in the behavioral response to cocaine and amphetamine. Implications for mechanisms mediating gender differences in drug abuse. Ann N Y Acad Sci 937:172–187

    Article  PubMed  CAS  Google Scholar 

  • Benstaali C, Mailloux A, Bogdan A, Auzeby A, Touitou Y (2001) Circadian rhythms of body temperature and motor activity in rodents their relationships with the light-dark cycle. Life Sci 68:2645–2656

    Article  PubMed  CAS  Google Scholar 

  • Berke JD, Hyman SE (2000) Addiction, dopamine, and the molecular mechanisms of memory. Neuron 25:515–532

    Article  PubMed  CAS  Google Scholar 

  • Berridge KC, Aldridge JW (2000a) Super-stereotypy I: enhancement of a complex movement sequence by systemic dopamine D1 agonists. Synapse 37:194–204

    Article  PubMed  CAS  Google Scholar 

  • Berridge KC, Aldridge JW (2000b) Super-stereotypy II: enhancement of a complex movement sequence by intraventricular dopamine D1 agonists. Synapse 37:205–215

    Article  PubMed  CAS  Google Scholar 

  • Bingham C, Arbogas A, Guillaume B (1982) Influential statistical methods for estimating and comparing cosine parameters. Chronobiologia 9:397–439

    PubMed  CAS  Google Scholar 

  • Bittman EL, Doherty L, Huang L, Paroskie A (2003) Period gene expression in mouse endocrine tissues. Am J Physiol Regul Integr Comp Physiol 285:561–569

    Google Scholar 

  • Boyson SJ, McGonigle P, Molinoff PB (1986) Quantitative autoradiographic localization of the D1 and D2 subtypes of dopamine receptors in rat brain. J Neurosci 6:3177–3188

    PubMed  CAS  Google Scholar 

  • Brandon CL, Steiner H (2003) Repeated methylphenidate treatment in adolescent rats alters gene regulation in the striatum. Eur J Neurosci 18:1584–1592

    Article  PubMed  Google Scholar 

  • Brandon CL, Marinelli M, Baker LK, White FJ (2001) Enhanced reactivity and vulnerability to cocaine following methylphenidate treatment in adolescent rats. Neuropsychopharmacology 25:651–661

    Article  PubMed  CAS  Google Scholar 

  • Camp DM, Robinson TE (1988) Susceptibility to sensitization. II. The influence of gonadal hormones on enduring changes in brain monoamines and behavior produced by the repeated administration of d-amphetamine or restraint stress. Behav Brain Res 30:69–88

    Article  PubMed  CAS  Google Scholar 

  • Cermakian N, Sassone-Corsi P (2002) Environmental stimulus perception and control of circadian clocks. Curr Opin Neurobiol 12:359–365

    Article  PubMed  CAS  Google Scholar 

  • Chartoff EH, Marck BT, Matsumoto AM, Dorse DM, Palmiter RD (2001) Induction of stereotypy in dopamine-deficient mice requires striatal D1 receptor activation. Proc Natl Acad Sci USA 98:10451–10456

    Article  PubMed  CAS  Google Scholar 

  • Chen CP, Kuhn P, Advis JP, Sarkar DK (2004) Chronic ethanol consumption impairs the circadian rhythm of pro-opiomelanocortin and period genes mRNA expression in the hypothalamus of the male rat. J Neurochem 88:1547–1554

    Article  PubMed  CAS  Google Scholar 

  • Dafny N, Yang PB (2006) The role of age, genotype, sex, and route of acute and chronic administration of methylphenidate: a review of its locomotor effects. Brain Res Bull 68:393–405

    Article  PubMed  CAS  Google Scholar 

  • Dazzi L, Seu E, Cherchi G, Barbieri PP, Matzeu A, Biggio G (2007) Estrous cycle-dependent changes in basal and ethanol-induced activity of cortical dopaminergic neurons in the rat. Neuropsychopharmacology 32:892–901

    Article  PubMed  CAS  Google Scholar 

  • Gadow KD (1997) An overview of three decades of research in pediatric psychopharmacoepidemiology. J Child Adolesc Psychopharmacol 7:219–236

    Article  PubMed  CAS  Google Scholar 

  • Gatley SJ, Volkow ND, Gifford AN, Fowler JS, Dewey SL, Ding YS, Logan J (1999) Dopamine-transporter occupancy after intravenous doses of cocaine and methylphenidate in mice and humans. Psychopharmacology (Berl) 146:93–100

    Article  CAS  Google Scholar 

  • Gaytan O, Ghelani D, Martin S, Swann A, Dafny N (1996) Dose response characteristics of methylphenidate on different indices of rats’ locomotor activity at the beginning of the dark cycle. Brain Res 727:13–21

    Article  PubMed  CAS  Google Scholar 

  • Gaytan O, al-Rahim S, Swann A, Dafny N (1997) Sensitization to locomotor effects of methylphenidate in the rat. Life Sci 61:101–107

    Article  Google Scholar 

  • Gaytan O, Lewis C, Swann A, Dafny N (1999) Diurnal differences in amphetamine sensitization. Eur J Pharmacol 374:1–9

    Article  PubMed  CAS  Google Scholar 

  • Gaytan O, Yang P, Swann A, Dafny N (2000) Diurnal differences in sensitization to methylphenidate. Brain Res 864:24–39

    Article  PubMed  CAS  Google Scholar 

  • Giros B, Jaber M, Jones SR, Wightman RM, Caron MG (1996) Hyperlocomotion and indifference to cocaine and amphetamine in mice lacking the dopamine transporter. Nature (Land) 379:606–612

    Article  CAS  Google Scholar 

  • Graybiel AM, Moratalla R, Robertson HA (1990) Amphetamine and cocaine induce drug-specific activation of the c-fos gene in striosome-matrix compartments and limbic subdivisions of the striatum. Proc Natl Acad Sci USA 87:6912–6916

    Article  PubMed  CAS  Google Scholar 

  • Greely H, Sahakian B, Harris J, Kessler RC, Gazzaniga M, Campbell P, Farah MJ (2008) Towards responsible use of cognitive-enhancing drugs by the healthy. Nature 456:702–705

    Article  PubMed  CAS  Google Scholar 

  • Griffin ML, Weiss RD, Mirin SM, Lange U (1989) A comparison of male and female cocaine abusers. Arch Gen Psychiatry 46:122–126

    PubMed  CAS  Google Scholar 

  • Heijtz RD, Beraki S, Scott L, Aperia A, Forssberg H (2002) Sex differences in the motor inhibitory and stimulatory role of dopamine D1 receptors in rats. Eur J Pharmacol 445:97–104

    Article  PubMed  CAS  Google Scholar 

  • Hyman SE, Malenka RC (2001) Addiction and the brain: the neurobiology of compulsion and its persistence. Nat Rev Neurosci 2:695–703

    Article  PubMed  CAS  Google Scholar 

  • Iijima M, Nikaido T, Akiyama M, Moriya T, Shibata S (2002) Methamphetamine-induced, suprachiasmatic nucleus-independent circadian rhythms of activity and mPer gene expression in the striatum of the mouse. Eur J Neurosci 16:921–929

    Article  PubMed  Google Scholar 

  • Ishida Y, Yokoyama C, Inatomi T, Yagita K, Dong X, Yan L, Yamaguchi S, Nagatsu I, Komori T, Kitahama K, Okamura H (2002) Circadian rhythm of aromatic L-amino acid decarboxylase in the rat suprachiasmatic nucleus: gene expression and decarboxylating activity in clock oscillating cells. Genes Cells 7:447–459

    Article  PubMed  CAS  Google Scholar 

  • Janssen BJA, Tyssen CM, Duindam H, Rietveld WJ (1994) Suprachiasmatic lesions eliminate 24-h blood pressure variability in rats. Physiol Behav 55:307–311

    Article  PubMed  CAS  Google Scholar 

  • Kalivas PW, Stewart J (1991) Dopamine transmission in the initiation and expression of drug- and stress-induced sensitization of motor activity. Brain Res Rev 16:223–244

    Article  PubMed  CAS  Google Scholar 

  • Kalivas PW, Duffy P, White SR (1998) MDMA elicits behavioral and neurochemical sensitization in rats. Neuropsychopharmacology 18:469–479

    Article  PubMed  CAS  Google Scholar 

  • Kollins SH, MacDonald EK, Rush CR (2001) Assessing the abuse potential of methylphenidate in nonhuman and human subjects: a review. Pharmacol Biochem Behav 68:611–627

    Article  PubMed  CAS  Google Scholar 

  • Kosobud AE, Pecoraro NC, Rebec GV, Timberlake W (1998) Circadian activity precedes daily methamphetamine injections in the rat. Neurosci Lett 250:99–102

    Article  PubMed  CAS  Google Scholar 

  • Kuczenski R, Segal DS (2001) Locomotor effects of acute and repeated threshold doses of amphetamine and methylphenidate: relative roles of dopamine and norepinephrine. J Pharmacol Exp Ther 296:876–883

    PubMed  CAS  Google Scholar 

  • Kuczenski R, Segal DS (2002) Exposure of adolescent rats to oral methylphenidate: preferential effects on extracellular norepinephrine and absence of sensitization and cross-sensitization to methamphetamine. J Neurosci 22:7264–7271

    PubMed  CAS  Google Scholar 

  • Lee MJ, Yang PB, Wilcox VT, Burau KD, Swann AC, Dafny N (2009) Does repetitive Ritalin injection produce long-term effects on SD female adolescent rats? Neuropharmacology 57:201–207

    Article  PubMed  CAS  Google Scholar 

  • Martin-Iverson MT, Iversen SD (1989) Day and night locomotor activity effects during administration of (+)-amphetamine. Pharmacol Biochem Behav 34:465–471

    Article  PubMed  CAS  Google Scholar 

  • Masubuchi S, Honma S, Abe H, Ishizaki K, Namihira M, Ikeda M, Honma K (2000) Clock genes outside the suprachiasmatic nucleus involved in manifestation of locomotor activity rhythm in rats. Eur J Neurosci 12:4206–4214

    PubMed  CAS  Google Scholar 

  • Mistlberger RE (2005) Circadian regulation of sleep in mammals: role of the suprachiasmatic nucleus. Brain Res Brain Res Rev 49:429–454

    Article  PubMed  Google Scholar 

  • Moore RY (1983) Organization and function of a central nervous system circadian oscillator: the suprachiasmatic hypothalamic nucleus. Fed Proc 42:2783–2789

    PubMed  CAS  Google Scholar 

  • Pelham WE, Gnagy EM, Burrows-Maclean L, Williams A, Fabiano GA, Morrisey SM, Chronis AM, Forehand GL, Nguyen CA, Hoffman MT, Lock TM, Fielbelkorn K, Coles EK, Panahon CJ, Steiner RL, Meichenbaum DL, Onyango AN, Morse GD (2001) Once-a-day Concerta methylphenidate versus three-times-daily methylphenidate in laboratory and natural settings. Pediatrics 107:E105

    Article  PubMed  CAS  Google Scholar 

  • Rivest R, Falardeau P, Di Paolo T (1995) Brain dopamine transporter: gender differences and effect of chronic haloperidol. Brain Res 692:269–272

    Article  PubMed  CAS  Google Scholar 

  • Rush CR, Baker RW (2001) Behavioral pharmacological similarities between methylphenidate and cocaine in cocaine abusers. Exp Clin Psychopharmacol 9:59–73

    Article  PubMed  CAS  Google Scholar 

  • Santosh PJ, Taylor E (2000) Stimulant drugs. Eur Child Adolesc Psychiatry 9:1–28

    Article  Google Scholar 

  • Scheel-Krüger J (1971) Comparative studies of various amphetamine analogues demonstrating different interactions with the metabolism of the catecholamines in the brain. Eur J Pharmacol 14:47–59

    Article  PubMed  Google Scholar 

  • Schindler CW, Carmona GN (2002) Effects of dopamine agonists and antagonists on locomotor activity in male and female rats. Pharmacol Biochem Behav 72:857–863

    Article  PubMed  CAS  Google Scholar 

  • Solanto MV (1998) Neuropsychopharmacological mechanisms of stimulant drug action in attention-deficit hyperactivity disorder: a review and integration. Behav Brain Res 94:127–152

    Article  PubMed  CAS  Google Scholar 

  • Solanto MV (2000) Clinical psychopharmacology of AD/HD: implications for animal models. Neurosci Biobehav Rev 24:27–30

    Article  PubMed  CAS  Google Scholar 

  • Stix G (2009) Turbocharging the brain. Sci Am 301(46–9):52–55

    Google Scholar 

  • Sujino M, Masumoto KH, Yamaguchi S, van der Horst GT, Okamura H, Inouye ST (2003) Suprachiasmatic nucleus grafts restore circadian behavioral rhythms of genetically arrhythmic mice. Curr Biol 13:664–668

    Article  PubMed  CAS  Google Scholar 

  • Terner JM, de Wit H (2006) Menstrual cycle phase and responses to drugs of abuse in humans. Drug Alcohol Depend 84:1–13

    Article  PubMed  CAS  Google Scholar 

  • Tornatzky W, Miczek KA (1999) Repeated limited access to i.v. cocaine self-administration: conditioned autonomic rhythmicity illustrating “predictive homeostasis”. Psychopharmacology (Berl) 145:144–152

    Article  CAS  Google Scholar 

  • Uz T, Ahmed R, Akhisaroglu M, Kurtuncu M, Imbesi M, Dirim Arslan A, Manev H (2005) Effect of fluoxetine and cocaine on the expression of clock genes in the mouse hippocampus and striatum. Neuroscience 134:1309–1316

    Article  PubMed  CAS  Google Scholar 

  • van Meel CS, Heslenfeld DJ, Oosterlaan J, Sergeant JA (2007) Adaptive control deficits in attention-deficit/hyperactivity disorder (ADHD): the role of error processing. Psychiatry Res 151:211–220

    Article  PubMed  Google Scholar 

  • Volkow ND, Wang GJ, Fowler JS, Logan J, Wong C, Hitzemann R, Pappas NR (1999) Reinforcing effects of psychostimulants in humans are associated with increases in brain dopamine and occupancy of D2 receptors. J Pharmacol Exp Ther 291:409–415

    PubMed  CAS  Google Scholar 

  • Weber M, Lanterburg T, Tobler I, Burgunder JM (2004) Circadian patterns of neurotransmitter related gene expression in motor regions of the rat brain. Neurosci Lett 358:17–20

    Article  PubMed  CAS  Google Scholar 

  • White SR, Yadao CM (2000) Characterization of methylphenidate exposures reported to a regional poison control center. Arch Pediatr Adolesc Med 154:1199–1203

    PubMed  CAS  Google Scholar 

  • Wilens TE, Adler LA, Adams J, Sgambati S, Rotrosen J, Sawtelle R, Utzinger L, Fusillo S (2008) Misuse and diversion of stimulants prescribed for ADHD: a systematic review of the literature. J Am Acad Child Adolesc Psychiatry 47:21–31

    Article  PubMed  Google Scholar 

  • Yamada N, Martin-Iverson MT (1991) Selective dopamine D1 and D2 agonists independently affect different components of the free-running circadian rhythm of locomotor activity in rats. Brain Res 538:310–312

    Article  PubMed  CAS  Google Scholar 

  • Yamazaki S, Numano R, Abe M, Hida A, Takahashi R, Ueda M, Block GD, Sakaki Y, Menaker M, Tei H (2000) Resetting central and peripheral circadian oscillators in transgenic rats. Science 288:682–685

    Article  PubMed  CAS  Google Scholar 

  • Yang P, Singhal N, Modi G, Swann A, Dafny N (2001) Effects of lithium chloride on induction and expression of methylphenidate sensitization. Eur J Pharmacol 426:65–72

    Article  PubMed  CAS  Google Scholar 

  • Yang PB, Amini B, Swann AC, Dafny N (2003) Strain differences in the behavioral responses of male rats to chronically administered methylphenidate. Brain Res 971:139–152

    Article  PubMed  CAS  Google Scholar 

  • Yang PB, Swann AC, Dafny N (2006) Acute and chronic methylphenidate dose-response experiment on three adolescent rat strains. Brain Res Bull 71:301–310

    Article  PubMed  CAS  Google Scholar 

  • Yang PB, Swann AC, Dafny N (2007) Chronic administration of methylphenidate produces neurophysiological and behavioral sensitization. Brain Res 1145:66–80

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We wish to thank Mallinckrodt, Inc. for its gift of methylphnidate. This research was supported in part by the Pat Rutherford Chair in Psychiatry and NIH R01 DA 027222.

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Authors and Affiliations

  1. Department of Neurobiology and Anatomy, The University of Texas Medical School at Houston, P.O. Box 20708, Houston, TX, 77225, USA

    Min J. Lee, Victor T. Wilcox & Nachum Dafny

  2. Department of Anatomy and Neurobiology, The University of California Irvine School of Medicine, Irvine, CA, 92697, USA

    Pamela B. Yang

  3. School of Public Health, Health Science Center at Houston, P.O. Box 20708, Houston, TX, 77225, USA

    Keith D. Burau

  4. Department of Psychiatry and Behavioral Sciences, The University of Texas Medical School at Houston, P.O. Box 20708, Houston, TX, 77225, USA

    Alan C. Swann & Nachum Dafny

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  1. Min J. Lee
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Correspondence to Nachum Dafny.

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Lee, M.J., Yang, P.B., Wilcox, V.T. et al. Repetitive methylphenidate administration modulates the diurnal behavioral activity pattern of adult female SD rats. J Neural Transm 118, 285–298 (2011). https://doi.org/10.1007/s00702-010-0510-8

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  • DOI: https://doi.org/10.1007/s00702-010-0510-8

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