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Chronic oral methylphenidate treatment increases microglial activation in rats

Journal of Neural Transmission volume 125, pages 1867–1875 (2018)Cite this article

Abstract

Methylphenidate (MP) is a widely prescribed psychostimulant used to treat attention deficit hyperactivity disorder. Previously, we established a drinking paradigm to deliver MP to rats at doses that result in pharmacokinetic profiles similar to treated patients. In the present study, adolescent male rats were assigned to one of three groups: control (water), low-dose MP (LD; 4/10 mg/kg), and high dose MP (HD; 30/60 mg/kg). Following 3 months of treatment, half of the rats in each group were euthanized, and the remaining rats received only water throughout a 1-month-long abstinence phase. In vitro autoradiography using [3H] PK 11195 was performed to measure microglial activation. HD MP rats showed increased [3H] PK 11195 binding compared to control rats in several cerebral cortical areas: primary somatosensory cortex including jaw (68.6%), upper lip (80.1%), barrel field (88.9%), and trunk (78%) regions, forelimb sensorimotor area (87.3%), secondary somatosensory cortex (72.5%), motor cortices 1 (73.2%) and 2 (69.3%), insular cortex (59.9%); as well as subcortical regions including the thalamus (62.9%), globus pallidus (79.4%) and substantia nigra (22.7%). Additionally, HD MP rats showed greater binding compared to LD MP rats in the hippocampus (60.6%), thalamus (59.6%), substantia nigra (38.5%), and motor 2 cortex (55.3%). Following abstinence, HD MP rats showed no significant differences compared to water controls; however, LD MP rats showed increased binding in pre-limbic cortex (78.1%) and ventromedial caudate putamen (113.8%). These findings indicate that chronic MP results in widespread microglial activation immediately after treatment and following the cessation of treatment in some brain regions.

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Funding

This research was funded by the New York Research Foundation [Q0942016] and the National Institute of Health [R01HD70888].

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Authors and Affiliations

  1. Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions (BNNLA), Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, 1021 Main St., Buffalo, NY, USA

    Emily Carias, John Hamilton & Panayotis K. Thanos

  2. Department of Neuroscience and Experimental Therapeutics, Albany Medical College, 47 New Scotland Ave., Albany, NY, USA

    Lisa S. Robison

  3. Department of Pharmacology, Medical School, University of Ioannina, 45110, Ioannina, Greece

    Foteini Delis

  4. Department of Psychology, University at Buffalo, 1021 Main St., Buffalo, NY, USA

    Rina Eiden

  5. Women and Children’s Hospital of Buffalo, Department of Pediatrics, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, USA

    Teresa Quattrin

  6. Department of Life Sciences, New York Institute of Technology, Northern Blvd., Old Westbury, NY, USA

    Michael Hadjiargyrou

  7. Department of Orthopedics, Stony Brook University, 100 Nicolls Rd., Stony Brook, NY, USA

    David Komatsu

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  1. Emily Carias
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Carias, E., Hamilton, J., Robison, L.S. et al. Chronic oral methylphenidate treatment increases microglial activation in rats. J Neural Transm 125, 1867–1875 (2018). https://doi.org/10.1007/s00702-018-1931-z

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