Advertisement

Psychopharmacology

, Volume 236, Issue 2, pp 685–698 | Cite as

Juvenile exposure to methylphenidate and guanfacine in rats: effects on early delay discounting and later cocaine-taking behavior

  • Nadja Freund
  • Chloe J. Jordan
  • Jodi L. Lukkes
  • Kevin J. Norman
  • Susan L. AndersenEmail author
Original Investigation
  • 182 Downloads

Abstract

Rationale

Both methylphenidate (MPH), a catecholamine reuptake blocker, and guanfacine, an alpha2A agonist, are used to treat attention-deficit hyperactivity disorder (ADHD). Childhood impulsivity, including delay discounting, is associated with increased substance use during adolescence. These effects can be mitigated by juvenile exposure to MPH, but less is known about the long-term effects of developmental exposure to guanfacine in males and females.

Objective

This study aims to determine sex differences and dose-dependent effects of juvenile exposure to MPH or guanfacine on delay-discounting and later cocaine self-administration.

Methods

The dose-dependent effects of vehicle, MPH (0.5, 1, and 2 mg/kg p.o.) or guanfacine (0.003, 0.03, and 0.3 mg/kg, i.p.) on discounting were determined in male and female Sprague-Dawley rats beginning at postnatal day (P)20. At P90, the amount, motivation, and sensitivity to cocaine following early drug exposure were determined with self-administration.

Results

Guanfacine, but not MPH, significantly reduced weight by 22.9 ± 4.6% in females. MPH dose dependently decreased delay discounting in both juvenile males and females, while guanfacine was only effective in males. Discounting was associated with cocaine self-administration in vehicle males (R2 = −0.4, P < 0.05) and self-administration was reduced by guanfacine treatment (0.3 mg/kg). Guanfacine significantly decreased cocaine sensitivity in both sexes.

Conclusions

These data suggest that MPH is effective in reducing delay discounting in both sexes. Due to both weight loss and ineffectiveness on discounting in females, guanfacine should be used only in males to reduce delay discounting and later cocaine use.

Keywords

Adolescence Cocaine Impulsive choice Intervention Prevention Substance use 

Notes

Author’s contributions

The following authors contributed in the following ways: NF and CJJ wrote the MatLab programs, ran animals, and helped write the manuscript; JLL and KJN treated and ran animals; and SLA designed the study, analyzed data, and wrote the manuscript.

Funding

The authors acknowledge the support of DA-10543, DA-026485, and MH 091114 (to SLA) and the technical assistance of Ms. Britta Thompson.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Disclosures

There are no competing financial interests in relation to the work described.

References

  1. Abela AR, Chudasama Y (2014) Noradrenergic alpha2A-receptor stimulation in the ventral hippocampus reduces impulsive decision-making. Psychopharmacology 231:521–531CrossRefGoogle Scholar
  2. Adriani W, Canese R, Podo F, Laviola G (2007) 1H MRS-detectable metabolic brain changes and reduced impulsive behavior in adult rats exposed to methylphenidate during adolescence. Neurotoxicol Teratol 29:116–125CrossRefGoogle Scholar
  3. Adriani W, Zoratto F, Laviola G (2012) Brain processes in discounting: consequences of adolescent methylphenidate exposure. Curr Top Behav Neurosci 9:113–143CrossRefGoogle Scholar
  4. Andersen SL (2005) Stimulants and the developing brain. Trends Pharmacol Sci 26:237–243CrossRefGoogle Scholar
  5. Andersen SL, Arvanitogiannis A, Pliakas AM, LeBlanc C, Carlezon WA Jr (2002) Altered responsiveness to cocaine in rats exposed to methylphenidate during development. Nat Neurosci 5:13–14CrossRefGoogle Scholar
  6. Anker JJ, Perry JL, Gliddon LA, Carroll ME (2009) Impulsivity predicts the escalation of cocaine selfadministration in rats. Pharmacol Biochem Behav 93:343–348CrossRefGoogle Scholar
  7. Arnsten AF (2009) Toward a new understanding of attention-deficit hyperactivity disorder pathophysiology: an important role for prefrontal cortex dysfunction. CNS drugs 23(Suppl 1):33–41CrossRefGoogle Scholar
  8. Bari A, Robbins TW (2013) Noradrenergic versus dopaminergic modulation of impulsivity, attention and monitoring behaviour in rats performing the stop-signal task: possible relevance to ADHD. PsychopharmacologyGoogle Scholar
  9. Barkley RA, Edwards G, Laneri M, Fletcher K, Metevia L (2001) Executive functioning, temporal discounting, and sense of time in adolescents with attention deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD). J Abnorm Child Psychol 29:541–556CrossRefGoogle Scholar
  10. Baskin BM, Dwoskin LP, Kantak KM (2015) Methylphenidate treatment beyond adolescence maintains increased cocaine self-administration in the spontaneously hypertensive rat model of attention deficit/hyperactivity disorder. Pharmacol Biochem Behav 131:51–56CrossRefGoogle Scholar
  11. Belin D, Belin-Rauscent A, Murray JE, Everitt BJ (2013) Addiction: failure of control over maladaptive incentive habits. Curr Opin Neurobiol 23:564–572CrossRefGoogle Scholar
  12. Berridge CW, Devilbiss DM, Andrzejewski ME, Arnsten AF, Kelley AE, Schmeichel B, Hamilton C, Spencer RC (2006) Methylphenidate preferentially increases catecholamine neurotransmission within the prefrontal cortex at low doses that enhance cognitive function. Biol Psychiatry 60:1111–1120CrossRefGoogle Scholar
  13. Biederman J, Faraone SV (2004) The Massachusetts General Hospital studies of gender influences on attention-deficit/hyperactivity disorder in youth and relatives. Psychiatr Clin North Am 27:225–232CrossRefGoogle Scholar
  14. Bizot JC, Chenault N, Houze B, Herpin A, David S, Pothion S, Trovero F (2007) Methylphenidate reduces impulsive behaviour in juvenile Wistar rats, but not in adult Wistar, SHR and WKY rats. Psychopharmacology 193:215–223CrossRefGoogle Scholar
  15. Bizot JC, David S, Trovero F (2011) Effects of atomoxetine, desipramine, d-amphetamine and methylphenidate on impulsivity in juvenile rats, measured in a T-maze procedure. Neurosci Lett 489:20–24CrossRefGoogle Scholar
  16. Boeck CR, Marques VB, Valvassori SS, Constantino LC, Rosa DV, Lima FF, Romano-Silva MA, Quevedo J (2009) Early long-term exposure with caffeine induces cross-sensitization to methylphenidate with involvement of DARPP-32 in adulthood of rats. Neurochem Int 55:318–322CrossRefGoogle Scholar
  17. Bolanos CA, Barrot M, Berton O, Wallace-Black D, Nestler EJ (2003) Methylphenidate treatment during pre- and periadolescence alters behavioral responses to emotional stimuli at adulthood. Biol Psychiatry 54:1317–1329CrossRefGoogle Scholar
  18. Brandon CL, Marinelli M, Baker LK, White FJ (2001) Enhanced reactivity and vulnerability to cocaine following methylphenidate treatment in adolescent rats. Neuropsychopharmacology 25:651–661CrossRefGoogle Scholar
  19. Brenhouse HC, Napierata L, Kussmaul L, Leussis M, Andersen SL (2009) Juvenile methylphenidate exposure and factors that influence incentive processing. Dev Neurosci 31:95–106CrossRefGoogle Scholar
  20. Bymaster FP, Katner JS, Nelson DL, Hemrick-Luecke SK, Threlkeld PG, Heiligenstein JH, Morin SM, Gehlert DR, Perry KW (2002) Atomoxetine increases extracellular levels of norepinephrine and dopamine in prefrontal cortex of rat. A potential mechanism for efficacy in attention deficit/hyperactivity disorder. Neuropsychopharmacology 27:699–711CrossRefGoogle Scholar
  21. Cavaliere C, Cirillo G, Bianco MR, Adriani W, De Simone A, Leo D, Perrone-Capano C, Papa M (2012) Methylphenidate administration determines enduring changes in neuroglial network in rats. Eur Neuropsychopharmacol 22:53–63CrossRefGoogle Scholar
  22. Crawford CA, Baella SA, Farley CM, Herbert MS, Horn LR, Campbell RH, Zavala AR (2011) Early methylphenidate exposure enhances cocaine self-administration but not cocaine-induced conditioned place preference in young adult rats. Psychopharmacology 213:43–52CrossRefGoogle Scholar
  23. Cross CP, Copping LT, Campbell A (2011) Sex differences in impulsivity: a meta-analysis. Psychol Bull 137:97–130CrossRefGoogle Scholar
  24. Dalley JW, Everitt BJ, Robbins TW (2011) Impulsivity, compulsivity, and top-down cognitive control. Neuron 69:680–694CrossRefGoogle Scholar
  25. Dalley JW, Robbins TW (2017) Fractionating impulsivity: neuropsychiatric implications. Nat Rev Neurosci 18:158–171CrossRefGoogle Scholar
  26. de Wit H (2009) Impulsivity as a determinant and consequence of drug use: a review of underlying processes. Addict Biol 14:22–31CrossRefGoogle Scholar
  27. Devoto P, Flore G, Pira L, Longu G, Gessa GL (2004) Alpha2-adrenoceptor mediated co-release of dopamine and noradrenaline from noradrenergic neurons in the cerebral cortex. J Neurochem 88:1003–1009CrossRefGoogle Scholar
  28. Diergaarde L, Pattij T, Poortvliet I, Hogenboom F, de Vries W, Schoffelmeer AN, De Vries TJ (2008) Impulsive choice and impulsive action predict vulnerability to distinct stages of nicotine seeking in rats. Biol Psychiatry 63:301–308CrossRefGoogle Scholar
  29. Doremus-Fitzwater TL, Barreto M, Spear LP (2012) Age-related differences in impulsivity among adolescent and adult Sprague-Dawley rats. Behav Neurosci 126:735–741CrossRefGoogle Scholar
  30. Ernst M, Zametkin AJ, Matochik JA, Jons PH, Cohen RM (1998) DOPA decarboxylase activity in attention deficit hyperactivity disorder adults. A [fluorine-18]fluorodopa positron emission tomographic study. J Neurosci 18:5901–5907CrossRefGoogle Scholar
  31. Eubig PA, Noe TE, Floresco SB, Sable JJ, Schantz SL (2014) Sex differences in response to amphetamine in adult Long-Evans rats performing a delay-discounting task. Pharmacol Biochem Behav 118(1–9)Google Scholar
  32. Floresco SB, Tse MT, Ghods-Sharifi S (2008) Dopaminergic and glutamatergic regulation of effort- and delay-based decision making. Neuropsychopharmacology 33:1966–1979CrossRefGoogle Scholar
  33. Fox AT, Hand DJ, Reilly MP (2008) Impulsive choice in a rodent model of attention-deficit/hyperactivity disorder. Behavioural brain research 187:146–152CrossRefGoogle Scholar
  34. Fox HC, Morgan PT, Sinha R (2014) Sex differences in guanfacine effects on drug craving and stress arousal in cocaine-dependent individuals. Neuropsychopharmacology 39:1527–1537CrossRefGoogle Scholar
  35. Fox HC, Seo D, Tuit K, Hansen J, Kimmerling A, Morgan PT, Sinha R (2012) Guanfacine effects on stress, drug craving and prefrontal activation in cocaine dependent individuals: preliminary findings. J Psychopharmacol 26:958–972CrossRefGoogle Scholar
  36. Freund N, MacGillivilray HT, Thompson BS, Lukkes JL, Stanis JJ, Brenhouse HC, Andersen SL (2014) Sex-dependent changes in ADHD-like behaviors in juvenile rats following cortical dopamine depletion. Behav Brain Res 270:357–363CrossRefGoogle Scholar
  37. Hains AB, Yabe Y, Arnsten AF (2015) Chronic Stimulation of Alpha-2A-Adrenoceptors With Guanfacine Protects Rodent Prefrontal Cortex Dendritic Spines and Cognition From the Effects of Chronic Stress. Neurobiology of stress 2:1–9CrossRefGoogle Scholar
  38. Hammerslag LR, Belagodu AP, Aladesuyi Arogundade OA, Karountzos AG, Guo Q, Galvez R, Roberts BW, Gulley JM (2017) Adolescent impulsivity as a sex-dependent and subtype-dependent predictor of impulsivity, alcohol drinking and dopamine D2 receptor expression in adult rats. Addict BiolGoogle Scholar
  39. Hammerslag LR, Waldman AJ, Gulley JM (2014) Effects of amphetamine exposure in adolescence or young adulthood on inhibitory control in adult male and female rats. Behav Brain Res 263:22–33CrossRefGoogle Scholar
  40. Hasnain M, Vieweg WV (2013) Weight considerations in psychotropic drug prescribing and switching. Postgrad Med 125:117–129CrossRefGoogle Scholar
  41. Jentsch JD, Sanchez D, Elsworth JD, Roth RH (2008) Clonidine and guanfacine attenuate phencyclidineinduced dopamine overflow in rat prefrontal cortex: mediating influence of the alpha-2A adrenoceptor subtype. Brain Res 1246:41–46CrossRefGoogle Scholar
  42. Jordan CJ, Andersen SL (2018) Working memory and salivary brain-derived neurotrophic factor as developmental predictors of cocaine seeking in males and females. Addict Biol 23:868–879CrossRefGoogle Scholar
  43. Juarez J, Guerrero-Alvarez A (2015) Effects of methylphenidate and atomoxetine on impulsivity and motor activity in preadolescent rats prenatally-treated with alcohol. Behavioral neuroscience 129:756–764CrossRefGoogle Scholar
  44. Khan MA, Jain G, Soltys SM, Takahashi A (2012) A case of excessive weight gain with guanfacine extended release: 9.53 kg in 4 weeks. J Child Adolesc Psychopharmacol 22:256–257CrossRefGoogle Scholar
  45. Khurana A, Romer D, Betancourt LM, Brodsky NL, Giannetta JM, Hurt H (2013) Working memory ability predicts trajectories of early alcohol use in adolescents: the mediational role of impulsivity. Addiction 108:506–515CrossRefGoogle Scholar
  46. Khurana A, Romer D, Betancourt LM, Brodsky NL, Giannetta JM, Hurt H (2014) Experimentation versus progression in adolescent drug use: a test of an emerging neurobehavioral imbalance model. Dev Psychopathol:1–13Google Scholar
  47. Khurana A, Romer D, Betancourt LM, Brodsky NL, Giannetta JM, Hurt H (2015) Experimentation versus progression in adolescent drug use: a test of an emerging neurobehavioral imbalance model. Dev Psychopathol 27:901–913CrossRefGoogle Scholar
  48. Khurana A, Romer D, Betancourt LM, Hurt H (2017) Working memory ability and early drug use progression as predictors of adolescent substance use disorders. Addiction 112:1220–1228CrossRefGoogle Scholar
  49. Kollins SH (2007) Abuse liability of medications used to treat attention-deficit/hyperactivity disorder (ADHD). The American Journal on Addictions/American Academy of Psychiatrists in Alcoholism and Addictions 16 Suppl 1: 35–42Google Scholar
  50. Koot S, van den Bos R, Adriani W, Laviola G (2009) Gender differences in delay-discounting under mild food restriction. Behav Brain Res 200:134–143CrossRefGoogle Scholar
  51. Larson EB, Graham DL, Arzaga RR, Buzin N, Webb J, Green TA, Bass CE, Neve RL, Terwilliger EF, Nestler EJ, Self DW (2011) Overexpression of CREB in the nucleus accumbens shell increases cocaine reinforcement in self-administering rats. J Neurosci 31:16447–16457CrossRefGoogle Scholar
  52. Lukkes JL, Freund N, Thompson BS, Meda S, Andersen SL (2016a) Preventative treatment in an animal model of ADHD: behavioral and biochemical effects of methylphenidate and its interactions with ovarian hormones in female rats. Eur Neuropsychopharmacol: the Journal of the European College of Neuropsychopharmacology 26:1496–1506CrossRefGoogle Scholar
  53. Lukkes JL, Thompson BS, Freund N, Andersen SL (2016b) The developmental inter-relationships between activity, novelty preferences, and delay discounting in male and female rats. Dev Psychobiol 58:231–242CrossRefGoogle Scholar
  54. Lynch WJ, Taylor JR (2005) Decreased motivation following cocaine self-administration under extended access conditions: effects of sex and ovarian hormones. Neuropsychopharmacology 30:927–935CrossRefGoogle Scholar
  55. Mannuzza S, Klein RG, Truong NL, Moulton JL 3rd, Roizen ER, Howell KH, Castellanos FX (2008) Age of methylphenidate treatment initiation in children with ADHD and later substance abuse: prospective follow-up into adulthood. Am J Psychiatry 165:604–609CrossRefGoogle Scholar
  56. Mar AC, Robbins TW (2007) Delay discounting and impulsive choice in the rat. Current protocols in neuroscience/editorial board, Jacqueline N Crawley [et al] Chapter 8: Unit 8, 22Google Scholar
  57. Martinez-Loredo V, Fernandez-Hermida JR, De La Torre-Luque A, Fernandez-Artamendi S (2018) Trajectories of impulsivity by sex predict substance use and heavy drinking. Addict Behav 85:164–172CrossRefGoogle Scholar
  58. Martinez-Raga J, Knecht C, de Alvaro R (2015) Profile of guanfacine extended release and its potential in the treatment of attention-deficit hyperactivity disorder. Neuropsychiatr Dis Treat 11:1359–1370CrossRefGoogle Scholar
  59. Marusich JA, Bardo MT (2009) Differences in impulsivity on a delay-discounting task predict selfadministration of a low unit dose of methylphenidate in rats. Behav Pharmacol 20:447–454CrossRefGoogle Scholar
  60. Milivojevic V, Fox HC, Jayaram-Lindstrom N, Hermes G, Sinha R (2017) Sex differences in guanfacine effects on stress-induced Stroop performance in cocaine dependence. Drug Alcohol Depend 179:275–279CrossRefGoogle Scholar
  61. Murray DW, Arnold LE, Swanson J, Wells K, Burns K, Jensen P, Hechtman L, Paykina N, Legato L, Strauss T (2008) A clinical review of outcomes of the multimodal treatment study of children with attention-deficit/hyperactivity disorder (MTA). Curr Psychiatry Rep 10:424–431CrossRefGoogle Scholar
  62. Newcorn JH, Halperin JM, Jensen PS, Abikoff HB, Arnold LE, Cantwell DP, Conners CK, Elliott GR, Epstein JN, Greenhill LL, Hechtman L, Hinshaw SP, Hoza B, Kraemer HC, Pelham WE, Severe JB, Swanson JM, Wells KC, Wigal T, Vitiello B (2001) Symptom profiles in children with ADHD: effects of comorbidity and gender. J Am Acad Child Adolesc Psychiatry 40:137–146CrossRefGoogle Scholar
  63. Pardey MC, Kumar NN, Goodchild AK, Cornish JL (2013) Catecholamine receptors differentially mediate impulsive choice in the medial prefrontal and orbitofrontal cortex. J Psychopharmacol 27:203–212CrossRefGoogle Scholar
  64. Perry JL, Carroll ME (2008) The role of impulsive behavior in drug abuse. Psychopharmacology 200:1–26CrossRefGoogle Scholar
  65. Perry JL, Larson EB, German JP, Madden GJ, Carroll ME (2005) Impulsivity (delay discounting) as a predictor of acquisition of IV cocaine self-administration in female rats. Psychopharmacology 178:193–201CrossRefGoogle Scholar
  66. Pietras CJ, Cherek DR, Lane SD, Tcheremissine OV, Steinberg JL (2003) Effects of methylphenidate on impulsive choice in adult humans. Psychopharmacology 170:390–398CrossRefGoogle Scholar
  67. Poulos CX, Le AD, Parker JL (1995) Impulsivity predicts individual susceptibility to high levels of alcohol self-administration. Behav Pharmacol 6:810–814CrossRefGoogle Scholar
  68. Rajala AZ, Jenison RL, Populin LC (2015) Decision making: effects of methylphenidate on temporal discounting in nonhuman primates. J Neurophysiol 114:70–79CrossRefGoogle Scholar
  69. Ramos BP, Stark D, Verduzco L, van Dyck CH, Arnsten AF (2006) Alpha2A-adrenoceptor stimulation improves prefrontal cortical regulation of behavior through inhibition of cAMP signaling in aging animals. Learn Mem 13: 770–776CrossRefGoogle Scholar
  70. Ren WW, Liu Y, Li BM (2012) Stimulation of alpha(2A)-adrenoceptors promotes the maturation of dendritic spines in cultured neurons of the medial prefrontal cortex. Mol Cell Neurosci 49:205–216CrossRefGoogle Scholar
  71. Richardson NR, Roberts DC (1996) Progressive ratio schedules in drug self-administration studies in rats: a method to evaluate reinforcing efficacy. J Neurosci Methods 66:1–11CrossRefGoogle Scholar
  72. Rose J, Otto T, Dittrich L (2008) The biopsychology-toolbox: a free, open-source MatLab-toolbox for the control of behavioral experiments. J Neurosci Methods 175:104–107CrossRefGoogle Scholar
  73. Rubia K, Taylor E, Smith AB, Oksanen H, Overmeyer S, Newman S, Oksannen H (2001) Neuropsychological analyses of impulsiveness in childhood hyperactivity. Br J Psychiatry J Ment Sci 179:138–143CrossRefGoogle Scholar
  74. Shansky RM, Hamo C, Hof PR, Lou W, McEwen BS, Morrison JH (2010) Estrogen promotes stress sensitivity in a prefrontal cortex-amygdala pathway. Cereb Cortex 20:2560–2567CrossRefGoogle Scholar
  75. Sher KJ, Bartholow BD, Wood MD (2000) Personality and substance use disorders: a prospective study. J Consult Clin Psychol 68:818–829CrossRefGoogle Scholar
  76. Shiels K, Hawk LW, Reynolds B, Mazzullo RJ, Rhodes JD, Pelham WE, Waxmonsky JG, Gangloff BP (2009) Effects of methylphenidate on discounting of delayed rewards in attention deficit/hyperactivity disorder. Exp Clin Psychopharmacol 17:291–301CrossRefGoogle Scholar
  77. Sikirica V, Haim Erder M, Xie J, Macaulay D, Diener M, Hodgkins P, Wu EQ (2012) Cost effectiveness of guanfacine extended release as an adjunctive therapy to a stimulant compared with stimulant monotherapy for the treatment of attention-deficit hyperactivity disorder in children and adolescents. PharmacoEconomics 30:e1–e15CrossRefGoogle Scholar
  78. Sillence MN, Tudor GD, Matthews ML, Lindsay DB (1992) Effects of the alpha 2-adrenoceptor agonist guanfacine on growth and thermogenesis in mice. J Anim Sci 70:3429–3434CrossRefGoogle Scholar
  79. Slezak JM, Anderson KG (2011) Effects of acute and chronic methylphenidate on delay discounting. Pharmacol Biochem Behav 99:545–551CrossRefGoogle Scholar
  80. Smethells JR, Swalve NL, Eberly LE, Carroll ME (2016) Sex differences in the reduction of impulsive choice (delay discounting) for cocaine in rats with atomoxetine and progesterone. Psychopharmacology 233:2999–3008CrossRefGoogle Scholar
  81. Smith RJ, Aston-Jones G (2011) Alpha(2) adrenergic and imidazoline receptor agonists prevent cue induced cocaine seeking. Biol Psychiatry 70:712–719CrossRefGoogle Scholar
  82. Somkuwar SS, Kantak KM, Bardo MT, Dwoskin LP (2016) Adolescent methylphenidate treatment differentially alters adult impulsivity and hyperactivity in the Spontaneously Hypertensive Rat model of ADHD. Pharmacol Biochem Behav 141:66–77CrossRefGoogle Scholar
  83. Staiti AM, Morgane PJ, Galler JR, Grivetti JY, Bass DC, Mokler DJ (2011) A microdialysis study of the medial prefrontal cortex of adolescent and adult rats. Neuropharmacology 61:544–549CrossRefGoogle Scholar
  84. Sun H, Cocker PJ, Zeeb FD, Winstanley CA (2012) Chronic atomoxetine treatment during adolescence decreases impulsive choice, but not impulsive action, in adult rats and alters markers of synaptic plasticity in the orbitofrontal cortex. Psychopharmacology 219:285–301CrossRefGoogle Scholar
  85. Thanos PK, Michaelides M, Benveniste H, Wang GJ, Volkow ND (2007) Effects of chronic oral methylphenidate on cocaine self-administration and striatal dopamine D2 receptors in rodents. Pharmacol Biochem Behav 87:426–433CrossRefGoogle Scholar
  86. Thomsen M, Caine SB (2005) Chronic intravenous drug self-administration in rats and mice. Current protocols in neuroscience/editorial board, Jacqueline N Crawley [et al] Chapter 9: Unit 9, 20Google Scholar
  87. Wargin W, Patrick K, Kilts C, Gualtieri CT, Ellington K, Mueller RA, Kraemer G, Breese GR (1983) Pharmacokinetics of methylphenidate in man, rat and monkey. J Pharmacol Exp Ther 226:382–386Google Scholar
  88. Weafer J, de Wit H (2014) Sex differences in impulsive action and impulsive choice. Addict Behav 39:1573–1579CrossRefGoogle Scholar
  89. Wilens TE, Biederman J, Martelon M, Zulauf C, Anderson JP, Carrellas NW, Yule A, Wozniak J, Fried R, Faraone SV (2016) Further evidence for smoking and substance use disorders in youth with bipolar disorder and comorbid conduct disorder. J Clin Psychiatry 77:1420–1427CrossRefGoogle Scholar
  90. Wilens TE, Faraone SV, Biederman J, Gunawardene S (2003) Does stimulant therapy of attentiondeficit/hyperactivity disorder beget later substance abuse? A meta-analytic review of the literature. Pediatrics 111:179–185CrossRefGoogle Scholar
  91. Winstanley CA (2011) The utility of rat models of impulsivity in developing pharmacotherapies for impulse control disorders. Br J Pharmacol 164:1301–1321CrossRefGoogle Scholar
  92. Winstanley CA, Theobald DE, Dalley JW, Cardinal RN, Robbins TW (2006) Double dissociation between serotonergic and dopaminergic modulation of medial prefrontal and orbitofrontal cortex during a test of impulsive choice. Cereb Cortex 16(1):106–114CrossRefGoogle Scholar
  93. Wolraich ML, Doffing MA (2004) Pharmacokinetic considerations in the treatment of attention-deficit hyperactivity disorder with methylphenidate. CNS Drugs 18:243–250CrossRefGoogle Scholar
  94. Yates JR, Perry JL, Meyer AC, Gipson CD, Charnigo R, Bardo MT (2014) Role of medial prefrontal and orbitofrontal monoamine transporters and receptors in performance in an adjusting delay discounting procedure. Brain Res 1574:26–36CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Laboratory of Developmental Neuropharmacology, McLean HospitalHarvard Medical SchoolBelmontUSA
  2. 2.Department of Psychiatry, McLean HospitalHarvard Medical SchoolBelmontUSA
  3. 3.Division of Experimental and Molecular PsychiatryLWL University Hospital BochumBochumGermany
  4. 4.Department of Psychiatry, Psychotherapy and Preventive MedicineRuhr-University BochumBochumGermany
  5. 5.Molecular Targets and Medications Discovery BranchNational Institute on Drug Abuse, Intramural Research ProgramBaltimoreUSA
  6. 6.Department of PsychiatryIndiana University School of MedicineIndianapolisUSA

Personalised recommendations