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The effects of adolescent methylphenidate self-administration on responding for a conditioned reward, amphetamine-induced locomotor activity, and neuronal activation

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Abstract

Background

Abuse of methylphenidate (Ritalin) is rising, particularly during adolescence and early adulthood, but the long-term effects of its abuse during adolescence are unclear.

Methods

In experiment 1, we examined the effect of adolescent methylphenidate self-administration (0.0625 mg/infusion), as compared with cocaine self-administration (0.125 mg/infusion), under a fixed ratio 1 schedule of reinforcement in male Sprague–Dawley rats during adolescence (postnatal day (PND) 32–47) on adult dopamine-mediated behaviors (PND >70). These included responding for a conditioned reward (CR), a measure of incentive motivation, and amphetamine-induced locomotor activity. In experiment 2, we aimed to replicate and enhance the effects observed in experiment 1, and we also examined the effects of methylphenidate self-administration during adolescence on adult amphetamine-induced zif268 messenger ribonucleic acid (mRNA) expression.

Results

Adolescent rats self-administered both cocaine and methylphenidate. There was no effect of adolescent drug self-administration on adult baseline or amphetamine-induced responding for a CR. However, both adolescent methylphenidate and cocaine self-administration increased amphetamine-induced locomotion. Adolescent methylphenidate self-administration also enhanced amphetamine-induced zif268 mRNA expression in the nucleus accumbens.

Conclusions

Our findings suggest that repeated, behaviorally contingent exposure to methylphenidate during adolescence enhances responsivity to the locomotor-stimulating and neuronal activating effects of amphetamine but not incentive motivation.

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Acknowledgments

The authors thank Drs. Suzanne Erb and Megan Shram for their advice on procedural aspects of this work and Judy Sinyard, Roger Raymond, Mustansir Diwan, and Silvia Isabella for technical assistance. This work was supported by a Masters Award from the Canadian Institutes of Health Research Masters Award to CLB and a Discovery Grant from Natural Sciences and Engeneering Research Council of Canada to PJF.

Ethical standards

Experiments were carried out in accordance with the Guide for the Care and Use of Laboratory Animals as adopted and promulgated by the National Institutes of Health. Procedures were approved by the CAMH Animal Care Committee.

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Authors and Affiliations

  1. Department of Psychology, University of Toronto, 100 St. George Street, Toronto, ON, Canada, M5S 3G3

    Christie L. Burton, José N. Nobrega & Paul J. Fletcher

  2. Section of Biopsychology, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON, Canada, M5T 1R8

    Christie L. Burton & Paul J. Fletcher

  3. Department of Pharmacology, University of Toronto, Toronto, ON, Canada

    José N. Nobrega

  4. Department of Psychiatry, University of Toronto, Toronto, ON, Canada

    José N. Nobrega & Paul J. Fletcher

  5. Section of Neuroimaging Research Section, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON, Canada, M5T 1R8

    José N. Nobrega

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  1. Christie L. Burton
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Correspondence to Christie L. Burton.

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Burton, C.L., Nobrega, J.N. & Fletcher, P.J. The effects of adolescent methylphenidate self-administration on responding for a conditioned reward, amphetamine-induced locomotor activity, and neuronal activation. Psychopharmacology 208, 455–468 (2010). https://doi.org/10.1007/s00213-009-1745-7

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