Methylphenidate administration determines enduring changes in neuroglial network in rats

Carlo Cavaliere, Giovanni Cirillo, Maria Rosaria Bianco, Walter Adriani, Antonietta De Simone, Damiana Leo, Carla Perrone-Capano, Michele Papa

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)53-63
Number of pages11
JournalEuropean Neuropsychopharmacology
Issue number1
Publication statusPublished - Jan 2012


  • ADHD
  • Drug addiction
  • Glutamate transporters
  • Methylphenidate
  • NNOS
  • Plasticity
  • Reactive astrocytosis

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health
  • Pharmacology (medical)
  • Biological Psychiatry
  • Neurology
  • Pharmacology


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