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Early methylphenidate exposure enhances cocaine self-administration but not cocaine-induced conditioned place preference in young adult rats

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Abstract

Rationale

Previous studies in rodents show that early exposure to methylphenidate alters later responsiveness to drugs of abuse. An interesting feature of these studies is that early methylphenidate treatment decreases the rewarding value of cocaine when measured by conditioned place preference (CPP), but the same treatment increases cocaine self-administration.

Objective

The goal of the present study was to examine the effects of early methylphenidate exposure on cocaine-induced responding using both reward paradigms.

Methods

Rats were treated with methylphenidate (0, 2, or 5 mg/kg) from postnatal days (PDs) 11 to 20, and then cocaine-induced CPP or cocaine self-administration was measured in separate groups of rats in adulthood. The CPP procedure included 8 days of acquisition training, 8 days of extinction training, and a reinstatement test. Rats were conditioned with 0, 10, or 20 mg/kg cocaine. Reinstatement was assessed after a priming dose of cocaine (10 mg/kg). For the self-administration experiment, a jugular catheter was implanted and rats were trained to press a lever reinforced with cocaine (0.25 or 0.75 mg/kg/infusion) on a fixed ratio (FR) one schedule. Rats were gradually moved from an FR1 to an FR10 schedule and, after criterion was reached, rats were placed on a progressive ratio schedule for 5 days.

Results

Cocaine produced robust rewarding effects as determined by both the CPP and self-administration experiments; however, early methylphenidate exposure only enhanced the reinforcing effects of cocaine on the self-administration paradigm. Interestingly, this methylphenidate enhancement was only seen in male rats.

Conclusions

These data suggest that in males, methylphenidate enhances the reinforcing value of cocaine, but not cocaine-associated cues.

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References

  • Achat-Mendes C, Anderson KL, Itzhak Y (2003) Methylphenidate and MDMA adolescent exposure in mice: long-lasting consequences on cocaine-induced reward and psychomotor stimulation in adulthood. Neuropharmacology 45:106–115

    Article  CAS  PubMed  Google Scholar 

  • Andersen SL (2003) Trajectories of brain development: point of vulnerability or window of opportunity? Neurosci Biobehav Rev 27:3–18

    Article  PubMed  Google Scholar 

  • Andersen SL (2005) Stimulants and the developing brain. Trends Pharmacol Sci 26:237–243

    Article  CAS  PubMed  Google Scholar 

  • 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 5:13–14

    Article  CAS  PubMed  Google Scholar 

  • Arnold S, Beyer C (2009) Neuroprotection by estrogen in the brain: the mitochondrial compartment as presumed therapeutic target. J Neurochem 111:1–11

    Article  Google Scholar 

  • Baker DA, Fuchs RA, Specio SE, Khroyan TV, Neisewander JL (1998) Effects of intraaccumbens administration of SCH-23390 on cocaine-induced locomotion and conditioned place preference. Synapse 30:181–193

    Article  CAS  PubMed  Google Scholar 

  • Balda MA, Anderson KL, Itzhak Y (2006) Adolescent and adult responsiveness to the incentive value of cocaine reward in mice: role of neuronal nitric oxide synthase (nNOS) gene. Neuropharmacology 51:341–349

    Article  CAS  PubMed  Google Scholar 

  • Banu SK, Govindarajulu P, Aruldhas MM (2002) Developmental profiles of TSH, sex steroids, and their receptors in the thyroid and their relevance to thyroid growth in immature rats. Steroids 67:137–144

    Article  CAS  PubMed  Google Scholar 

  • Bardo MT, Bevins RA (2000) Conditioned place preference: what does it add to our preclinical understanding of drug reward? Psychopharmacology (Berl) 153:31–43

    Article  CAS  Google Scholar 

  • Bardo MT, Rowlett JK, Harris MJ (1995) Conditioned place preference using opiate and stimulant drugs: a meta-analysis. Neurosci Biobehav Rev 19:39–51

    Article  CAS  PubMed  Google Scholar 

  • Biederman J, Farone S (2005) Attention-deficit hyperactivity disorder. Lancet 366:237–248

    Article  PubMed  Google Scholar 

  • Bloom B, Cohen RA, Freeman G (2009) Summary health statistics for U.S. children: national health interview survey, 2007. Vital Health Stat 239:1–88

    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  CAS  PubMed  Google Scholar 

  • Brann DW, Dhandapani K, Wakade C, Mahesh V, Khan MM (2007) Neurotropic and neuroprotective actions of estrogen: basic mechanisms and clinical implications. Steroids 72:381–405

    Article  CAS  PubMed  Google Scholar 

  • Brown TE, Lee BR, Sorg BA (2008) The NMDA antagonist MK-801 disrupts reconsolidation of a cocaine-associated memory for conditioned place preference but not for self-administration in rats. Learn Mem 15:857–865

    Article  PubMed  Google Scholar 

  • Campbell J, Spear LP (1999) Effects of early handling on amphetamine-induced locomotor activation and conditioned place preference in the adult rat. Psychopharmacology (Berl) 143:183–189

    Article  CAS  Google Scholar 

  • Carlezon WA Jr, Mague SD, Andersen SL (2003) Enduring behavioral effects of early exposure to methylphenidate in rats. Biol Psychiatry 54:1317–1329

    Article  Google Scholar 

  • Cervo L, Samanin R (1995) Effects of dopaminergic and glutamatergic receptor antagonists on the acquisition and expression of cocaine conditioning place preference. Brain Res 673:242–250

    Article  CAS  PubMed  Google Scholar 

  • Crawford CA, Villafranca SW, Cyr MC, Farley CM, Reichel CM, Gheorghe SL, Krall CM, McDougall SA (2007) Effects of early methylphenidate exposure on morphine- and sucrose-reinforced behaviors in adult rats: relationship to dopamine D2 receptors. Brain Res 1139:245–253

    Article  CAS  PubMed  Google Scholar 

  • Crawford CA, McDougall SA, Bolanos CA, Hall S, Berger SP (1995) The effects of the kappa agonist U-50,488 on cocaine-induced conditioned and unconditioned behaviors and Fos immunoreactivity. Psychopharmacology (Berl) 120:392–399

    Article  CAS  Google Scholar 

  • Crawford CA, McDougall SA, Meier TL, Collins RL, Watson JB (1998) Repeated methylphenidate treatment induces behavioral sensitization and decreases protein kinase A and dopamine-stimulated adenylyl cyclase activity in the dorsal striatum. Psychopharmacology (Berl) 136:23–43

    Article  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  CAS  PubMed  Google Scholar 

  • Dopheide JA, Pliszka SR (2009) Attention-deficit-hyperactivity disorder: an update. Pharmacotherapy 29:658–679

    Article  Google Scholar 

  • Gaytan O, Al-Rahim S, Swann A, Dafny N (1997) Sensitization to locomotor effects of methylphenidate in the rat. Life Sci 61:PL101–PL107

    Article  CAS  PubMed  Google Scholar 

  • Gerasimov MR, Franceschi M, Volkow ND, Gifford A, Gatley SJ, Marsteller D, Molina PE, Dewey SL (2000) Comparison between intraperitoneal and oral methylphenidate administration: microdialysis and locomotor activity study. J Pharmacol Exp Ther 295:51–57

    CAS  PubMed  Google Scholar 

  • Halladay LR, Iñiguez SD, Furqan F, Previte MC, Chisum AM, Crawford CA (2009) Methylphenidate potentiates morphine-induced antinociception, hyperthermia, and locomotor activity in young adult rats. Pharmacol Biochem Behav 92:190–196

    Article  CAS  PubMed  Google Scholar 

  • Kosten TA, Zhang XY, Kehoe P (2006) Heightened cocaine and food self-administration in female rats with neonatal isolation experience. Neuropsychopharmacology 31:70–76

    Article  CAS  PubMed  Google Scholar 

  • Liu Y, Roberts DCS, Morgan D (2005) Sensitization of the reinforcing effects of self-administered cocaine in rats: effects of dose and intravenous injection speed. Eur J Neurosci 22:195–200

    Article  PubMed  Google Scholar 

  • Lu L, Shepard JD, Hall FS, Shaham Y (2003) Effect of environmental stressors on opiate and psychostimulant reinforcement, reinstatement and discrimination in rats: a review. Neurosci Biobehav Rev 27:457–491

    Article  CAS  PubMed  Google Scholar 

  • Lu L, Dempsey J, Shaham Y, Hope BT (2005) Differential long-term neuroadaptations of glutamate receptors in the basolateral and central amygdala after withdrawal from cocaine self-administration in rats. J Neurochem 94:161–168

    Article  CAS  PubMed  Google Scholar 

  • Mandt BH, Schenk S, Zahniser NR, Allen RM (2008) Individual differences in cocaine-induced locomotor activity in male Sprague–Dawley rats and their acquisition of and motivation to self administer cocaine. Psychopharmacology (Berl) 201:195–202

    Article  CAS  Google Scholar 

  • McDougall SA, Reichel CM, Farley CM, Flesher MM, Der-Ghazarian T, Cortez AM, Wacan JJ, Martinez CE, Varela FA, Butt AE, Crawford CA (2008) Postnatal manganese exposure alters dopamine transporter function in adult rats: potential impact on nonassociative and associative processes. Neuroscience 154:846–860

    Article  Google Scholar 

  • National Research Council (2003) Guidelines for the care and use mammals in neuroscience and behavioral research. National Academy, Washington DC

  • Pierce RC, Kalivas RW (1997) A circuitry model of the expression of behavioral sensitization to amphetamine-like psychostimulants. Brain Res Rev 25:193–216

    Article  Google Scholar 

  • Robinson TE, Berridge KC (1993) The neural basis of drug craving: an incentive-sensitization theory of addiction. Brain Res Rev 18:247–291

    Article  CAS  PubMed  Google Scholar 

  • Robinson TE, Berridge KC (2000) The psychology and neurobiology of addiction: an incentive-sensitization view. Addiction 95:s91–s117

    PubMed  Google Scholar 

  • Russo SJ, Jenab S, Fabian SJ, Festa ED, Kemen LM, Quinones-Jenab V (2003) Sex differences in the conditioned rewarding effects of cocaine. Brain Res 38:214–220

    Article  Google Scholar 

  • Scheffler RM, Brown TT, Fulton BD, Hinshaw SP, Levine P, Stone S (2009) Positive association between attention-deficit/hyperactivity disorder medication use and academic achievement during elementary school. Pediatrics 123:1273–1279

    Article  PubMed  Google Scholar 

  • Souza RP, Soares EC, Rosa DV, Souza BR, Réus GZ, Barichello T, Gomes KM, Gomez MV, Quevedo J, Romano-Silva MA (2008) Methylphenidate alters NCS-1 expression in rat brain. Neurochem Int 53:12–16

    Article  CAS  PubMed  Google Scholar 

  • Sproson EJ, Chantrey J, Hollis C, Marsden CA, Fone KCF (2001) Effect of repeated methylphenidate administration on presynaptic dopamine and behavior in young adult rats. J Psychopharmacol 152:67–75

    Article  Google Scholar 

  • Swanson JM, Wigal SB, Wigal T, Sonuga-Barke E, Greenhill LL, Biederman J, Kollins S, Nguyen AS, DeCory HH, Dirksen SJH, Hatch S, Comacs Study Group (2004) A comparison of once-daily extended-release methylphenidate formulations in children with attention-deficit/hyperactivity disorder in the laboratory school (The Comacs Study). Pediatrics 113:e206–e216

    Article  PubMed  Google Scholar 

  • Wigal SB, Gupta S, Greenhill L, Posner K, Lerner M, Steinhoff K, Wigal T, Kapelinski A, Martinez J, Modi NB, Stehli A, Swanson J (2007) Pharmacokinetics of methylphenidate in preschoolers with attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol 17:153–164

    Article  PubMed  Google Scholar 

  • Yano M, Steiner H (2007) Methylphenidate and cocaine: the same effects on gene regulation? Trends Pharmacol Sci 28:588–596

    Article  CAS  PubMed  Google Scholar 

  • Zakharova E, Wade D, Izenwasser S (2009) Sensitivity to cocaine conditioned reward depends on sex and age. Pharmacol Biochem Behav 92:131–134

    Article  CAS  PubMed  Google Scholar 

  • Zavala AR, Biswas S, Harlan RE, Neisewander JL (2007) Fos and glutamate AMPA receptor subunit coexpression associated with cue-elicited cocaine-seeking behavior in abstinent rats. Neuroscience 145:438–452

    Article  CAS  PubMed  Google Scholar 

  • Zavala AR, Osredkar T, Joyce JN, Neisewander JL (2008a) Upregulation of Arc mRNA expression in the prefrontal cortex following cue-induced reinstatement of extinguished cocaine-seeking behavior. Synapse 62:421–431

    Article  CAS  Google Scholar 

  • Zavala AR, Browning JR, Dickey ED, Biswas S, Neisewander JL (2008b) Region-specific involvement of AMPA/Kainate receptors in Fos protein expression induced by cocaine-conditioned cues. Eur Neuropsychopharmacol 18:600–611

    Article  CAS  Google Scholar 

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Acknowledgments

We gratefully acknowledge Dr. Janet Neisewander for her substantial assistance with the self-administration procedure. We also thank Dr. Sanders McDougall for his meticulous editing of the manuscript. This work was supported by PHS grant GM073842.

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Authors and Affiliations

  1. Department of Psychology, California State University, San Bernardino, CA, 92407, USA

    Cynthia A. Crawford, Shelley A. Baella, Cristal M. Farley, Matthew S. Herbert, Leslie R. Horn & Rachel H. Campbell

  2. Department of Psychology, California State University, Long Beach, CA, 90840, USA

    Arturo R. Zavala

Authors
  1. Cynthia A. Crawford
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  2. Shelley A. Baella
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  3. Cristal M. Farley
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  4. Matthew S. Herbert
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  6. Rachel H. Campbell
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  7. Arturo R. Zavala
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Correspondence to Cynthia A. Crawford.

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Crawford, C.A., Baella, S.A., Farley, C.M. et al. Early methylphenidate exposure enhances cocaine self-administration but not cocaine-induced conditioned place preference in young adult rats. Psychopharmacology 213, 43–52 (2011). https://doi.org/10.1007/s00213-010-2011-8

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  • DOI: https://doi.org/10.1007/s00213-010-2011-8

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