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20.09.2018 | Psychiatry and Preclinical Psychiatric Studies - Original Article

Chronic oral methylphenidate treatment increases microglial activation in rats

verfasst von: Emily Carias, John Hamilton, Lisa S. Robison, Foteini Delis, Rina Eiden, Teresa Quattrin, Michael Hadjiargyrou, David Komatsu, Panayotis K. Thanos

Erschienen in: Journal of Neural Transmission | Ausgabe 12/2018

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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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Titel: Chronic oral methylphenidate treatment increases microglial activation in rats
verfasst von: Emily Carias
John Hamilton
Lisa S. Robison
Foteini Delis
Rina Eiden
Teresa Quattrin
Michael Hadjiargyrou
David Komatsu
Panayotis K. Thanos
Publikationsdatum: 20.09.2018
Verlag: Springer Vienna
Erschienen in: Journal of Neural Transmission / Ausgabe 12/2018
Print ISSN: 0300-9564
Elektronische ISSN: 1435-1463
DOI: https://doi.org/10.1007/s00702-018-1931-z

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Chronic oral methylphenidate treatment increases microglial activation in rats

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