title: Chronic oral methylphenidate treatment reversibly increases striatal dopamine transporter and dopamine type 1 receptor binding in rats.
abstract: Previously, we created an 8-h limited-access dual bottle drinking paradigm to deliver methylphenidate (MP) to rats at two dosages that result in a pharmacokinetic profile similar to patients treated for attention deficit hyperactivity disorder. Chronic treatment resulted in altered behavior, with some effects persisting beyond treatment. In the current study, adolescent male Sprague-Dawley rats were split into three groups at four weeks of age: control (water), low-dose MP (LD), and high-dose MP (HD). Briefly, 4 mg/kg (low dose; LD) or 30 mg/kg (high dose; HD) MP was consumed during the first hour, and 10 mg/kg (LD) or 60 mg/kg (HD) MP during hours two through eight. Following three months of treatment, half of the rats in each group (n = 8-9/group) were euthanized, and remaining rats went through a 1-month abstinence period, then euthanized. In vitro receptor autoradiography was performed to quantify binding levels of dopamine transporter (DAT), dopamine type 1 (D1R)-like receptors, and dopamine type 2 (D2R)-like receptors using [3H] WIN35,428, [3H] SCH23390, and [3H] Spiperone, respectively. Immediately following treatment, HD MP-treated rats had increased DAT and D1R-like binding in several subregions of the basal ganglia, particularly more caudal portions of the caudate putamen, which correlated with some previously reported behavioral changes. There were no differences between treatment groups in any measure following abstinence. These findings suggest that chronic treatment with a clinically relevant high dose of MP results in reversible changes in dopamine neurochemistry, which may underlie some effects on behavior.
authors.affiliation: Department of Psychology, Stony Brook University, 100 Nicolls Road, Stony Brook, NY, 11794, USA.
authors.forename: Lisa S
authors.initials: LS
authors.lastname: Robison
authors.affiliation: Department of Neurobiology, Stony Brook University, 100 Nicolls Road, Stony Brook, NY, 11794, USA.
authors.forename: Mala
authors.initials: M
authors.lastname: Ananth
authors.affiliation: Department of Life Sciences, New York Institute of Technology, Northern Boulevard, P.O. Box 8000, Old Westbury, NY, 11568, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Hadjiargyrou
authors.affiliation: Department of Orthopedics, Stony Brook University, 100 Nicolls Road, Stony Brook, NY, 11794, USA.
authors.forename: David E
authors.initials: DE
authors.lastname: Komatsu
authors.affiliation: Behavioral Neuropharmacology and Neuroimaging Laboratory On Addictions, Research Institute On Addictions, University at Buffalo, 1021 Main St, Buffalo, NY, 14203, USA. pthanos@ria.buffalo.edu.
authors.forename: Panayotis K
authors.initials: PK
authors.lastname: Thanos
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001345:Autoradiography; D001552:Benzazepines; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003042:Cocaine / Q000031:analogs & derivatives; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D015259:Dopamine Agents; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology*; D019275:Radiopharmaceuticals; D011918:Rats, Inbred SHR; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D013134:Spiperone; D014316:Tritium
chemical_list: D001552:Benzazepines; D000697:Central Nervous System Stimulants; C000607792:DRD2 protein, rat; D015259:Dopamine Agents; D050483:Dopamine Plasma Membrane Transport Proteins; D019275:Radiopharmaceuticals; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C534628:SCH 23390; D014316:Tritium; D008774:Methylphenidate; D013134:Spiperone; C021279:(1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester; D003042:Cocaine
keywords: Dopamine; Methylphenidate; Psychostimulant; Reward deficiency syndrome, reward, addiction; Transporter