title: The Impact of Chronic Early Administration of Psychostimulants on Brain Expression of BDNF and Other Neuroplasticity-Relevant Proteins.
abstract: Frequently, healthy individuals, children, and students are using stimulants to treat attention deficit hyperactivity disorder (ADHD)-like symptoms or to enhance cognitive capacity, attention and concentration. Methylphenidate, the most common treatment for ADHD, similarly to cocaine, blocks the dopamine reuptake, leading to increase in dopamine level in the synaptic cleft. Brain-derived neurotrophic factor (BDNF) and other neuroplasticity-relevant proteins have a major role in cellular plasticity during development and maturation of the brain. Young Sprague Dawley rats (postnatal days (PND) 14) were treated chronically with either cocaine or methylphenidate. The rats were examined behaviorally and biochemically at several time points (PND 35, 56, 70, and 90). We found age-dependent, but stimulant-independent, alterations in the mRNA expression levels of microtubule-associated protein tau, doublecortin, and synaptophysin. The PND 90 rats, treated with methylphenidate at an early age, exhibited increased BDNF protein levels in the prefrontal cortex compared to the saline-treated group. Despite the treatment effects at the biochemical level, cocaine and methylphenidate treatments at an early age had only minor effects on the behavioral parameters measured at older ages. The biochemical alterations may reflect neuroprotective or neuroplastic effects of chronic methylphenidate treatment at an early age.
authors.affiliation: Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv, 69978, Tel-Aviv, Israel.
authors.forename: Yaarit
authors.initials: Y
authors.lastname: Simchon Tenenbaum
authors.affiliation: Research Unit, Geha Mental Health Center and Felsenstein Medical Research Center, Petah-Tikva, Israel.
authors.forename: Abraham
authors.initials: A
authors.lastname: Weizman
authors.affiliation: Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv, 69978, Tel-Aviv, Israel. mrehavi@post.tau.ac.il.|The Dr. Miriam and Sheldon G. Adelson Chair and Center for the Biology of Addictive Diseases, Tel-Aviv, Israel. mrehavi@post.tau.ac.il.
authors.forename: Moshe
authors.initials: M
authors.lastname: Rehavi
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000494:pharmacology*; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage / Q000494:pharmacology*; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D009473:Neuronal Plasticity / Q000187:drug effects; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016708:Synaptophysin / Q000235:genetics / Q000378:metabolism; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D000697:Central Nervous System Stimulants; C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D016708:Synaptophysin; D016875:tau Proteins; D008774:Methylphenidate; D003042:Cocaine
keywords: Attention deficit hyperactivity disorder (ADHD); Brain-derived neurotrophic factor (BDNF); Cocaine; Doublecortin (DCX); Methylphenidate (MPH)