title: Methylphenidate administration determines enduring changes in neuroglial network in rats.
abstract: Repeated exposure to psychostimulant drugs induces complex molecular and structural modifications in discrete brain regions of the meso-cortico-limbic system. This structural remodeling is thought to underlie neurobehavioral adaptive responses. Administration to adolescent rats of methylphenidate (MPH), commonly used in attention deficit and hyperactivity disorder (ADHD), triggers alterations of reward-based behavior paralleled by persistent and plastic synaptic changes of neuronal and glial markers within key areas of the reward circuits. By immunohistochemistry, we observe a marked increase of glial fibrillary acidic protein (GFAP) and neuronal nitric oxide synthase (nNOS) expression and a down-regulation of glial glutamate transporter GLAST in dorso-lateral and ventro-medial striatum. Using electron microscopy, we find in the prefrontal cortex a significant reduction of the synaptic active zone length, paralleled by an increase of dendritic spines. We demonstrate that in limbic areas the MPH-induced reactive astrocytosis affects the glial glutamatergic uptake system that in turn could determine glutamate receptor sensitization. These processes could be sustained by NO production and synaptic rearrangement and contribute to MPH neuroglial induced rewiring.
authors.affiliation: Department of Medicina Pubblica Clinica e Preventiva, Second University of Naples, Naples, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Cavaliere
authors.forename: Giovanni
authors.initials: G
authors.lastname: Cirillo
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Bianco
authors.forename: Walter
authors.initials: W
authors.lastname: Adriani
authors.forename: Antonietta
authors.initials: A
authors.lastname: De Simone
authors.forename: Damiana
authors.initials: D
authors.lastname: Leo
authors.forename: Carla
authors.initials: C
authors.lastname: Perrone-Capano
authors.forename: Michele
authors.initials: M
authors.lastname: Papa
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D002755:Choice Behavior / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D008774:Methylphenidate / Q000494:pharmacology*; D009415:Nerve Net / Q000187:drug effects* / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012201:Reward
chemical_list: D000697:Central Nervous System Stimulants; D005904:Glial Fibrillary Acidic Protein; D008774:Methylphenidate; D052248:Nitric Oxide Synthase Type I