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Adolescent Exposure to Methylphenidate Increases Impulsive Choice Later in Life


Adolescent Exposure to Methylphenidate Increases Impulsive Choice Later in Life

Abbas, Zarish, Sweet, Arwen, Hernandez, Giovanni and Arvanitogiannis, Andreas (2017) Adolescent Exposure to Methylphenidate Increases Impulsive Choice Later in Life. Frontiers in Behavioral Neuroscience, 11 (214). pp. 1-8. ISSN 1662-5153

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Official URL: http://dx.doi.org/10.3389/fnbeh.2017.00214


Background: The psychostimulant methylphenidate (MPH) is known to temporarily reduce impulsive choice and promote self-control. What is not sufficiently understood is how repeated treatment with MPH affects impulsive choice in the long run, and whether any such effect is contingent on exposure at certain developmental stages.
Methods: Using an animal model for impulsive choice, we examined first whether giving MPH through early adolescence alters delay discounting, an operational measure of impulsive choice, later in adulthood. We then tested whether equivalent long-term effects are observed if exposure to the drug occurred during adulthood. Starting on postnatal day 25 or postnatal day 60, male rats received one of a range of doses of MPH for 10 consecutive days. Twenty-six days later, all rats were trained to choose between a lever that produced a small immediate reward and a lever that produced a large reward after a range of delays.
Results: Rats showed a long-term decrease in the selection of the delayed larger reward when treated with moderate doses of MPH during early adolescence, but not when treated with the lower or higher doses. In contrast, no differences were observed in the selection of the delayed larger reward in animals that were treated with various doses of MPH during adulthood.
Conclusions: Our findings suggest effects of MPH on impulsive choice that are contingent on dosage and on the developmental period of exposure. When administered during adolescence, moderate doses of MPH increase impulsive choice long after the end of treatment, whereas these same doses administered during adulthood were without effect

Divisions:Concordia University > Faculty of Arts and Science > Psychology
Item Type:Article
Authors:Abbas, Zarish and Sweet, Arwen and Hernandez, Giovanni and Arvanitogiannis, Andreas
Journal or Publication:Frontiers in Behavioral Neuroscience
Date:31 October 2017
  • Concordia Open Access Author Fund
  • Natural Sciences and Engineering Research Council of Canada Discovery Grant (# 249848-2007)
Digital Object Identifier (DOI):10.3389/fnbeh.2017.00214
Keywords:ritalin, delay discounting, impulsivity, adolescence, rats, long-term effects
ID Code:983226
Deposited On:23 Nov 2017 13:25
Last Modified:18 Jan 2018 17:56


Adriani, W., Canese, R., Podo, F., and Laviola, G. (2007). 1H MRS-detectable metabolic brain changes and reduced impulsive behavior in adult rats exposed to methylphenidate during adolescence. Neurotoxicol. Teratol. 29, 116–125. doi: 10.1016/j.ntt.2006.11.010

Ainslie, G. (1975). Specious reward: a behavioral theory of impulsiveness and impulse control. Psychol. Bull. 82, 463–496. doi: 10.1037/h0076860

Andersen, S. L., Arvanitogiannis, A., Pliakas, A. M., LeBlanc, C., and Carlezon, W. A. (2002). Altered responsiveness to cocaine in rats exposed to methylphenidate during development. Nat. Neurosci. 5, 13–14. doi: 10.1038/nn777

Benes, F. M., Vincent, S. L., Molloy, R., and Khan, Y. (1996). Increased interaction of dopamine-immunoreactive varicosities with GABA neurons of rat medial prefrontal cortex occurs during the postweanling period. Synapse 23, 237–245. doi: 10.1002/(SICI)1098-2396(199608)23:4<237::AID-SYN1>3.0.CO;2-8

Bolaños, C. A., Barrot, M., Berton, O., Wallace-Black, D., and Nestler, E. J. (2003). Methylphenidate treatment during pre- and periadolescence alters behavioral responses to emotional stimuli at adulthood. Biol. Psychiatry 54, 1317–1329. doi: 10.1016/S0006-3223(03)00570-5

Brandon, C. L., Marinelli, M., and White, F. J. (2003). Adolescent exposure to methylphenidate alters the activity of rat midbrain dopamine neurons. Biol. Psychiatry 54, 1338–1344. doi: 10.1016/S0006-3223(03)00787-X

Burgos, H., Cofré, C., Hernández, A., Sáez-Briones, P., Agurto, R., Castillo, A., et al. (2015). Methylphenidate has long-lasting metaplastic effects in the prefrontal cortex of adolescent rats. Behav. Brain Res. 291, 112–117. doi: 10.1016/j.bbr.2015.05.009

Carlezon, W. A., Mague, S. D., Andersen, S. L., and Carlezon, B. (2003). Enduring behavioral effects of early exposure to methylphenidate in rats. Biol. Psychiatry 54, 1330–1337. doi: 10.1016/j.biopsych.2003.08.020

Cheng, J., Xiong, Z., Duffney, L. J., Wei, J., Liu, A., Liu, S., et al. (2014). Methylphenidate exerts dose-dependent effects on glutamate receptors and behaviors. Biol. Psychiatry 76, 953–962. doi: 10.1016/j.biopsych.2014.04.003

Crowley, N. A., Cody, P. A., Davis, M. I., Lovinger, D. M., and Mateo, Y. (2014). Chronic methylphenidate exposure during adolescence reduces striatal synaptic responses to ethanol. Eur. J. Neurosci. 39, 548–556. doi: 10.1111/ejn.12426

Devilbiss, D. M., and Berridge, C. W. (2008). Cognition-Enhancing doses of methylphenidate preferentially increase prefrontal cortex neuronal responsiveness. Biol. Psychiatry 64, 626–635. doi: 10.1016/j.biopsych.2008.04.037

Evenden, J. L., and Ryan, C. N. (1996). The pharmacology of impulsive behaviour in rats: the effects of drugs on response choice with varying delays of reinforcement. Psychopharmacology (Berl) 128, 161–170. doi: 10.1007/s002130050121

Giedd, J. N., Blumenthal, J., Jeffries, N. O., Castellanos, F. X., Liu, H., Zijdenbos, A., et al. (1999). Brain development during childhood and adolescence: a longitudinal MRI study. Nat. Neurosci. 2, 861–863. doi: 10.1038/13158

Gogtay, N., Giedd, J. N., Lusk, L., Hayashi, K. M., Greenstein, D., Vaituzis, A. C., et al. (2004). Dynamic mapping of human cortical development during childhood through early adulthood. Proc. Natl. Acad. Sci. U.S.A. 101, 8174–8179. doi: 10.1073/pnas.0402680101

Hernandez, G., Oleson, E. B., Gentry, R. N., Abbas, Z., Bernstein, D. L., Arvanitogiannis, A., et al. (2014). Endocannabinoids promote cocaine-induced impulsivity and its rapid dopaminergic correlates. Biol. Psychiatry 75, 487–498. doi: 10.1016/j.biopsych.2013.09.005

Kheramin, S., Body, S., Ho, M. Y., Velázquez-Martinez, D. N., Bradshaw, C. M., Szabadi, E., et al. (2004). Effects of orbital prefrontal cortex dopamine depletion on inter-temporal choice: a quantitative analysis. Psychopharmacology (Berl) 175, 206–214. doi: 10.1007/s00213-004-1813-y

Koob, G. F., and Le Moal, M. (1997). Drug abuse: hedonic homeostatic dysregulation. Science 278, 52–58.

Leo, D., Adriani, W., Cavaliere, C., Cirillo, G., Marco, E. M., Romano, E., et al. (2009). Methylphenidate to adolescent rats drives enduring changes of accumbal Htr7 expression: implications for impulsive behavior and neuronal morphology. Genes Brain Behav. 8, 356–368. doi: 10.1111/j.1601-183X.2009.00486.x

Low, K. G., and Gendaszek, A. E. (2010). Illicit use of psychostimulants among college students: a preliminary study. Psychol. Heal Med. 7, 283–287. doi: 10.1080/13548500220139386

Manitt, C., Mimee, A., Eng, C., Pokinko, M., Stroh, T., Cooper, H. M., et al. (2011). The netrin receptor DCC is required in the pubertal organization of mesocortical dopamine circuitry. J. Neurosci. 31, 8381–8394. doi: 10.1523/JNEUROSCI.0606-11.2011

Moll, G. H., Hause, S., Rüther, E., Rothenberger, A., and Huether, G. (2001). Early methylphenidate administration to young rats causes a persistent reduction in the density of striatal dopamine transporters. J. Child Adolesc. Psychopharmacol. 11, 15–24. doi: 10.1089/104454601750143366

Naneix, F., Marchand, A. R., Di Scala, G., Pape, J. R., and Coutureau, E. (2012). Parallel maturation of goal-directed behavior and dopaminergic systems during adolescence. J. Neurosci. 32, 16223–16232. doi: 10.1523/JNEUROSCI.3080-12.2012

Pardey, M. C., Kumar, N. N., Goodchild, A. K., Clemens, K. J., Homewood, J., and Cornish, J. L. (2012). Long-Term effects of chronic oral ritalin administration on cognitive and neural development in adolescent wistar kyoto rats. Brain Sci. 2, 375–404. doi: 10.3390/brainsci2030375

Pietras, C. J., Cherek, D. R., Lane, S. D., Tcheremissine, O. V., and Steinberg, J. L. (2003). Effects of methylphenidate on impulsive choice in adult humans. Psychopharmacology (Berl) 170, 390–398. doi: 10.1007/s00213-003-1547-2

Pine, A., Shiner, T., Seymour, B., and Dolan, R. J. (2010). Dopamine, time, and impulsivity in humans. J. Neurosci. 30, 8888–8896. doi: 10.1523/JNEUROSCI.6028-09.2010

Pitts, R. C., and McKinney, A. P. (2005). Effects Of methylphenidate and morphine on delay-discount functions obtained within sessions. J. Exp. Anal. Behav. 83, 297–314. doi: 10.1901/jeab.2005.47-04

Rachlin, H. (2006). Notes on discounting. J. Exp. Anal. Behav. 85, 425–435. doi: 10.1901/jeab.2006.85-05

Rachlin, H., Green, L., and Vi, A. D. (1972). Commitment, choice and self-control. Exp. Anal. Behav. 17, 15–22.

Reynolds, L. M., Makowski, C. S., Yogendran, S. V., et al. (2015). Amphetamine in adolescence disrupts the development of medial prefrontal cortex dopamine connectivity in a dcc-dependent manner. Neuropsychopharmacology 40, 1101–1112. doi: 10.1038/npp.2014.287

Richards, J. B., Mitchell, S. H., de Wit, H., and Seiden, L. S. (1997). Determination of discount functions in rats with an adjusting-amount procedure. J. Exp. Anal. Behav. 67, 353–366. doi: 10.1901/jeab.1997.67-353

Shiels, K., Hawk, L. W., Reynolds, B., Mazzullo, R. J., Rhodes, J. D., Pelham, W. E., et al. (2009). Effects of methylphenidate on discounting of delayed rewards in attention deficit/hyperactivity disorder. Exp. Clin. Psychopharmacol. 17, 291–301. doi: 10.1037/a0017259

Somkuwar, S. S., Jordan, C. J., Kantak, K. M., and Dwoskin, L. P. (2013). Adolescent atomoxetine treatment in a rodent model of ADHD: effects on cocaine self-administration and dopamine transporters in frontostriatal regions. Neuropsychopharmacology 38, 2588–2597. doi: 10.1038/npp.2013.163

Spear, L. P. (2000). The adolescent brain and age-related behavioral manifestations. Neurosci. Biobehav. Rev. 24, 417–463 doi: 10.1016/S0149-7634(00)00014-2

Urban, K. R., and Gao, W. J. (2015). Evolution of the study of methylphenidate and its actions on the adult versus juvenile brain. J. Atten. Disord. 19, 603–619. doi: 10.1177/1087054712455504

van der Marel, K., Klomp, A., Meerhoff, G. F., Schipper, P., Lucassen, P. J., Homberg, J. R., et al. (2014). Long-term oral methylphenidate treatment in adolescent and adult rats: differential effects on brain morphology and function. Neuropsychopharmacology 39, 263–273. doi: 10.1038/npp.2013.169

van Gaalen, M. M., van Koten, R., Schoffelmeer, A. N. M., and Vanderschuren, L. J. M. J. (2006). Critical involvement of dopaminergic neurotransmission in impulsive decision making. Biol. Psychiatry 60, 66–73. doi: 10.1016/j.biopsych.2005.06.005

Vendruscolo, L. F., Izídio, G. S., Takahashi, R. N., and Ramos, A. (2008). Chronic methylphenidate treatment during adolescence increases anxiety-related behaviors and ethanol drinking in adult spontaneously hypertensive rats. Behav. Pharmacol. 19, 21–27. doi: 10.1097/FBP.0b013e3282f3cfbe

Winstanley, C. A. (2010). “The neural and neurochemical basis of delay discounting,” in Impulsivity: The Behavioral and Neurological Science of Discounting, eds G. J. Madden and W. K. Bickel (Washington, DC: American Psychological Association), 95–121. doi: 10.1037/12069-004

Zeeb, F. D., Floresco, S. B., and Winstanley, C. A. (2010). Contributions of the orbitofrontal cortex to impulsive choice: interactions with basal levels of impulsivity, dopamine signalling, and reward-related cues. Psychopharmacology (Berl) 211, 87–98. doi: 10.1007/s00213-010-1871-2

Zosel, A., Bartelson, B. B., Bailey, E., Lowenstein, S., and Dart, R. (2013). Characterization of adolescent prescription drug abuse and misuse using the researched abuse diversion and addiction-related surveillance (RADARS®) system. J. Am. Acad. Child Adolesc. Psychiatry 52, 196–204. doi: 10.1016/j.jaac.2012.11.014
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